Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)
Phase: PHASE1
Conditions: Corona Virus Infection, ARDS, ARDS, Human, Acute Respiratory Distress Syndrome, COVID-19
Sponsor: Camillo Ricordi

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
1 | P a g e  
 
 
C o nfi de ntial
  
 
 
Di visi o n of C ell ul ar Tr a ns pl a nt ati o n, D e p art m e nt of S ur g er y  
U ni v ersit y of Mi a mi L e o n ar d M. Mill er Sc h o ol of M e dici n e 
 
 
 
U m bilic al C or d- d eri v e d M es e nc h y m al St e m C ells f or C O VI D- 1 9 P ati e nts 
wit h Ac ut e R es pir at or y Distr ess S y n dr o m e ( A R D S) 
 
 
N ati o n al Cli nic al Tri al ( N C T) I d e ntifi er N u m b er:  N C T 0 4 3 5 5 7 2 8 
Pr ot oc ol N u m b er: E pr ost 2 0 2 0 0 6 7 1 
S h ort Titl e: U C- M S Cs i n C O VI D- 1 9 
V ersi o n N u m b er:  v 8 dt 0 2. 1 2. 2 0 2 1 
I N D N u m b er: 1 9 7 5 7 
 
S P O N S O R-I N V E S TI G A T O R 
C a mill o Ric or di, M. D., F N AI 
 
 
  
Di a b et es R es e arc h I nstit ut e C ell Tr a ns pl a nt C e nt er 
Di visi o n of C ell ul ar Tr a ns pl a nt ati o n, D e p art m e nt of S ur g er y 
U ni v ersit y of Mi a mi Mill er Sc h o ol of M e dici n e  
1 4 5 0 N W 1 0t h A v e n u e, Mi a mi, FL 3 3 1 3 6 
Offic e: 3 0 5 2 4 3- 6 9 1 3; F ax: 3 0 5 2 4 3- 4 4 0 4 
 
 
C o nfi d e nti al 
 

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P R E F A C E 
T h e cli nic al Pr ot oc ol U M BILI C AL C O R D- D E RI V E D M E S E N C H Y M AL S T E M C ELL S F O R C O VI D- 1 9 P A TI E N T S WI T H A C U T E 
R E S PI R A T O R Y DI S T R E S S  S Y N D R O M E ( A R D S) ( U C- M S Cs i n C O VI D- 1 9), d escri b es t h e b ac k gr o u n d, d esi g n, a n d or g a niz ati o n 
of t his e arl y p h as e cli nic al tri al.  T h e Di a b et es R es e arc h I n stit ut e C ell Tr a ns pl a nt C e nt er will m ai nt ai n t h e pr ot oc ol o v er 
t h e c o urs e of t h e st u d y t hr o u g h n e w r el e as es of t h e pr ot oc ol, or iss u a nc e of u p d at es eit h er i n t h e f or m of r e visi o ns of 
c o m pl et e c h a pt ers or p a g es t h er e of, or i n t h e f or m of s u p pl e m e nt al pr ot oc ol m e m or a n d a. 
 
C O N T RI B U T O R S : G I A C O M O LA N Z O NI 1 A, E LI N A LI N E T S K Y1 A, D I E G O C O R R E A 1 A, R O G E R A.  A L V A R E Z 1 B,  2, A N T O NI O M A R T T O S 2, 3, A N D R E W A. R.  
P A S T E W S KI 3, E N RI Q U E G I N Z B U R G3, K H E M R AJ H I R A NI1 B, S H A RI M E S SI N G E R C A Y E T A N O 1 A, M I C H A EL JO H N P AI D A S 2, JO N ELL E F A N TI S P O T T E R 2, 
X I U MI N X U 1 A, M A RIL Y N G L A S S B E R G 4, JI A N MI N G T A N 5, N O R M A S U E K E N Y O N 1 A, D A VI D B AI D AL 1 B, R O D OL F O A L EJ A N D R O 1 B, R O D RI G O V I A N N A 
2, 6, 7, LI S A R A F KI N 1 B, R A F F A ELL A P O G GI OLI 1 A, P HILLI P R UI Z 2, 6, 7, A R N OL D I. C A PL A N 8, C A MILL O R I C O R DI1, 2, 6    
1)  
1 AD I A B E T E S R E S E A R C H IN S TI T U T E , C ELL T R A N S PL A N T C E N T E R , U NI V E R SI T Y O F M I A MI M ILL E R S C H O OL O F M E DI CI N E , FL,  U. S. A.   
1 B D I A B E T E S R E S E A R C H IN S TI T U T E , D E P T O F M E DI CI N E , U NI V E R SI T Y O F M I A MI M ILL E R S C H O OL O F M E DI CI N E , FL,  U. S. A. 
2)  U H E AL T H - U NI V E R SI T Y O F M I A MI H E AL T H S Y S T E M , FL,  U. S. A. 
3)  
 JA C K S O N H E AL T H S Y S T E M , FL,  U. S. A.  
4)  U NI V E R SI T Y O F A RI Z O N A C OLL E G E O F M E DI CI N E , A Z,  U. S. A. 
5)  F U Z H O U G E N E R AL H O S PI T AL , C HI N A  
6)  D E P A R T M E N T O F S U R G E R Y , U NI V E R SI T Y O F M I A MI M ILL E R S C H O OL O F M E DI CI N E , FL,  U. S. A.  
7)  M I A MI T R A N S PL A N T IN S TI T U T E , JA C K S O N H E AL T H S Y S T E M , FL,  U. S. A.  
8)  C A S E W E S T E R N R E S E R V E U NI V E R SI T Y , C L E V EL A N D, O H,  U. S. A.  

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C o nfi de ntial
  
 

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I N V E S TI G A T O R’ S A G R E E M E N T 
 
I h a v e r ec ei v e d a n d r e a d t h e Cli nic al Pr ot oc ol U m bilic al C or d- d eri v e d M es e nc h y m al St e m  C ells f or C O VI D- 1 9 P ati e nts 
wit h Ac ut e R es pir at or y Distr ess S y n dr o m e ( A R D S) ( V ersi o n 8, d at e d 0 2. 1 2. 2 0 2 1)  
I a gr e e t o c o n d uct t h e st u d y as o utli n e d a n d t o m ai nt ai n t h e c o nfi d e nti alit y of all i nf or m at i o n r ec ei v e d or d e v el o p e d i n 
c o n n ecti o n wit h t his pr ot oc ol. 
 
Pri nt e d N a m e of I n v esti g at or 
 
Si g n at ur e of I n v esti g at or 
 
D at e ( D D/ M M M/ Y Y Y Y) 
 
 
 

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D O C U M E N T HI S T O R Y S U M M A R Y 
D oc u m e nt
 D at e
 
Ori gi n al Pr ot oc ol ( V ersi o n 1 dt. M arc h 1 1,  2 0 2 0) 
Tr e at m e nt pr ot oc ol i n 1 2 s u bj ects  
V ersi o n 2 dt. 0 4. 0 8. 2 0 2 0 
R a n d o miz e d, o p e n l a b el tri al t o ev al u at e pri m arily s af ety 
a n d s ec o n d ar y ex pl or at ory effic acy e n d p oi nts of all o g e n eic 
U C- M S C i n C O VI D- 1 9 p ati e nts wit h A R D S, wit h t w o gr o u ps: 
tr e at m e nt gr o u p ( n = 1 2) w h er e t h e s u bj ects will r ec eiv e U C-
M S C i nv esti g ati o n al pr o d uct (I P) a n d st a n d ar d of c ar e ( b est 
s u p p orti n g c ar e), a n d c o ntr ol gr o u p ( n = 1 2) 
V ersi o n 3 dt. 0 4. 3 0. 2 0 2 0 
C o ntr ol gr o u p ( n = 1 2)  will r ec eiv e t w o i nf usi o ns of v e hicl e 
a n d st a n d ar d of c ar e ( b est s u p p ortiv e c ar e). 
V ersi o n 4 dt. 0 5. 2 0. 2 0 2 0 
Ex p a n d e d eli gi bilit y crit eri a a n d a d d e d m ulti-sit e 
c o m p o n e nt t o t h e pr ot oc ol wit h a d d e d c e nt ers.  
 
V ersi o n 5 dt.  0 6. 0 4. 2 0 2 0 
U p d at e d sc h e d ul e of  ass ess m e nt ( m ai nly a d diti o n of Vir al 
L o a d by S A R S- C o V- 2 R T- P C R a n d k e e pi n g s m ell 
i d e ntific ati o n t est o pti o n al b as e d o n p ati e nt c o n diti o n, 
etc). U p d at e d tr e at m e nt of st u dy s u bj ects acc or di n g t o 
est a blis h e d b est pr actic e st a n d ar ds of c ar e wit h p artic ul ar 
att e nti o n t o v e ntil at or w e a ni n g a n d ass ess m e nt of 
r e a di n ess f or ext u b ati o n t o i m pr ov e c o nsist e ncy a m o n g 
st u dy sit es a n d pr o d uc e r eli a bly i nt er pr et a bl e r es ults.  
V ersi o n 6 dt.  0 6. 1 3. 2 0 2 0  
 
 
P ers o n n el C h a n g e a n d mi n or e dits, i ncl u di n g gr a m m atic al 
u p d at e a n d r e m ov al of r e p etitiv e i nf or m ati o n 
 
V ersi o n 7 dt. 0 7. 0 7. 2 0 2 0 
E dits i n I ncl usi o n cr it eri a, Sc h e d ul e of Ass ess m e nt, c h a n g e 
i n Al b u mi n ( 1 t o 1 0 %) i n I P, P ers o n n el c h a n g e  
V ersi o n 8 dt. 0 2. 1 2. 2 0 2 1 
S p ecifyi n g d oc u m e nt ati o n of m e di c ati o n r ec or ds i n e C R F 
t h at ar e r el at e d t o C O VI D- 1 9 a n d st ori n g all ot h er 
m e dic ati o ns i n r es e arc h r ec or ds.  

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T a bl e of C o nt e nts 
I N V E S TI G A T O R’ S A G R E E ME N T ...................................................................................................... .......................................... 4 
St at e m e nt of C o m pli a nc e ....................................................................................................... ................................................ 8 
S y n o psis....................................................................................................................... ............................................................ 9 
I ncl usi o n Crit eri a ............................................................................................................................................................... 1 1 
E xcl usi o n Crit eri a  .............................................................................................................................................................. 1 1 
A bstr act ...................................................................................................................... ........................................................... 1 3 
P u blic H e alt h R el e v a nc e St at e m e nt ............................................................................................. ..................................... 1 3 
Ex ec uti v e S u m m ar y ............................................................................................................. .................................................. 1 4 
Pr o bl e m ....................................................................................................................... ...................................................... 1 4 
R es e arc h H y p ot h esis ........................................................................................................... .............................................. 1 4 
R ati o n al e ..................................................................................................................... ...................................................... 1 4 
I m p ort a nc e of t h e R es earc h..................................................................................................... ......................................... 1 5 
O bj ectiv es .................................................................................................................... .......................................................... 1 5 
Pri m ar y o b j ecti v e .............................................................................................................................................................. 1 5 
S ec o n d ar y o b j ecti v e .......................................................................................................................................................... 1 5 
S p ecific Ai ms ................................................................................................................. ........................................................ 1 5 
S p ecific Ai m 1 ................................................................................................................ .................................................... 1 5 
S p ecific Ai m 2 ................................................................................................................ .................................................... 1 6 
B ac k gr o u n d .................................................................................................................... ....................................................... 1 6 
R es e arc h str at e g y ............................................................................................................. ..................................................... 1 8 
Si g nific a nc e .................................................................................................................. ..................................................... 1 8 
I n n o v ati o n ......................................................................................................................................................................... 1 9 
( 3 8- 4 0) ( 2 6, 3 1, 3 2, 3 8- 4 0, 4 2, 5 1, 5 9) St u d y D esi g n a n d M et h o ds ....................................................................................... 1 9 
R es e arc h T e a m: ................................................................................................................ ................................................. 1 9 
Cli nic al Tr i al D esi g n ........................................................................................................................................................... 2 5 
S u bj ect S e l ecti o n ............................................................................................................................................................... 2 5 
I ncl usi o n Crit eri a ............................................................................................................................................................... 2 5 
Excl usi o n Cr it eri a ............................................................................................................................................................... 2 6 
St u d y E n d p oi nts ............................................................................................................... ................................................. 2 6 
Pri m ar y E n d p oi nts: ............................................................................................................ ............................................ 2 6 
S ec o n d ar y E n d p oi nts: .......................................................................................................... ......................................... 2 7 
St u d y Pr oc e d ur es: St u d y d esi g n, i ncl u di n g t h e s e q u e nc e a n d ti mi n g of st u d y pr oc e d ur es ......................................... .... 2 8 
St u d y d ur ati o n a n d n u m b er of st u d y visits  r e q uir e d of r es e arc h p artici p a nts. ................................................................ 3 0 

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C o nfi de ntial
  
Bli n di n g, i ncl u di n g j ustific ati o n f or bli n di n g or  n ot bli n di n g t h e tri al, if a p plic a bl e. ......................................................... 3 0 
J ustific ati o n of w h y p artici p a nts will n ot r ec ei v e r outi n e c ar e or will h a v e c urr e nt t h er a p y st o p p e d. ......................... ... 3 1 
J ustific ati o n f or i ncl usi o n of a plac e b o or n o n-tr e a t m e nt gr o u p. ..................................................................................... 3 1 
D efi niti o n of tr e at m e nt f ail ur e or  p artici p a nt r e m ov al crit eri a. .............................................................. ......................... 3 1 
D escri pti o n of w h at h a p p e ns t o p artici p a nts r ec ei vi n g t h er a p y w h e n st u d y e n ds or if a p artici p a nt’s p artici p ati o n i n t h e 
st u d y e n ds pr e m at ur el y. ....................................................................................................... ............................................ 3 1 
S u bj ect P o p ul ati o n ................................................................................................................................................................ 3 1 
I n v esti g ati o n al Pr od uct ....................................................................................................... .................................................. 3 2 
C h ar act eriz ati o n a n d p h ysic al pr o p erti es ...................................................................................... ................................... 3 3 
Pr e p ar ati o n f or A d mi nist r ati o n of U C- M S C: ..................................................................................... ................................ 3 3 
U C- M S C D os e J ustific ati o n a n d C ell I nf usi o n: .................................................................................. ................................. 3 4 
F aciliti es a n d R es o urc es: ..................................................................................................... .............................................. 3 5 
c G M P A d v a nc e d C ell a n d Bi ol o gic Pr o d ucts M a n uf act uri n g F acilit y ............................................................... ............. 3 5 
St u d y St atistics .............................................................................................................. ........................................................ 3 5 
Pri m ar y o utc o m e v ari a bl es ..................................................................................................... ...................................... 3 5 
S ec o n d ar y o utc o m e v ari a bl es ................................................................................................... .................................... 3 6 
Ris ks ......................................................................................................................... ............................................................. 3 6 
St e ps t a k e n t o mi ni miz e t h e ris ks. ............................................................................................ .................................... 3 7 
U n a ntici p at e d pr o bl e ms ........................................................................................................ ........................................... 3 7 
Pl a n f or r e p orti n g u n a ntici p at e d pr o bl e ms or st u d y  d e vi ati o ns. ..................................................................................... 3 7 
Scr e e n F ail ur es ............................................................................................................... ............................................... 3 8 
Wit h dr a w al Crit eri a  a n d Pr oc e d ur es ............................................................................................................................ 3 8 
Miss e d Cli nic  Visits ........................................................................................................................................................ 3 8 
Pr ot oc ol D e vi ati o ns ........................................................................................................... ............................................ 3 8 
Pr e m at ur e E n d of St u d y ........................................................................................................ ........................................ 3 9 
M e dic ati o n C h a n g es............................................................................................................. ......................................... 3 9 
U n bli n di n g .................................................................................................................... ................................................. 3 9 
B e n efits ...................................................................................................................... ........................................................... 3 9 
A dv ers e E v e nts ................................................................................................................ ...................................................... 3 9 
E v al u ati o n of A d v ers e E v e nts: ................................................................................................. .......................................... 3 9 
D efi niti o ns ( a d v er s e e v e nts): ........................................................................................................................................ 3 9 
Ass ess m e nt of  S af et y ............................................................................................................................................................ 4 2 
Pri m ar y S af et y  E n d p oi nt ................................................................................................................................................... 4 2 
D at a S af et y a n d S u p er visi o n ................................................................................................... .......................................... 4 2 
St o p pi n g R ul es ................................................................................................................ ................................................... 4 2 
R e p orts a n d R ec or d s M a n a g e m e nt ...................................................................................................................................... 4 3 

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I n v esti g at or R ec or ds ......................................................................................................................................................... 4 4 
I n v esti g at or R e p orts .......................................................................................................................................................... 4 4 
D at a C oll ecti o n: .............................................................................................................. ................................................... 4 4 
S o urc e D o c u m e nts .............................................................................................................. .............................................. 4 5 
R ec or ds R et e nti o n at  t h e St u d y Sit e ................................................................................................................................. 4 5 
P a y m e nt a n d R e m u n er ati o n ...................................................................................................... ....................................... 4 5 
C osts ......................................................................................................................... ......................................................... 4 5 
D at a M a n a g e m e nt ............................................................................................................... ............................................. 4 5 
St atistic al A n al ysis .......................................................................................................... ................................................... 4 5 
S a m pl e Siz e C o nsi d er ati o ns: ................................................................................................... ...................................... 4 6 
St u d y Or g a niz ati o n a n d A d mi nistr ati o n ......................................................................................... ................................... 4 6 
D at a M a n a g e m e nt ............................................................................................................... ............................................. 4 7 
R e g ul at or y, Et hic al, a n d St u d y  O v ersi g ht C o nsi d er ati o ns ..................................................................................................... 4 7 
St u d y Disc o nti n u ati o n a n d Cl os ur e ............................................................................................. .......................................... 4 7 
C o nfi d e nti alit y a n d Pri v ac y ................................................................................................... ................................................ 4 8 
F ut ur e Us e of St or e d S p eci m e ns a n d D at a ....................................................................................... .................................... 4 9 
S af et y O v ersi g ht .............................................................................................................. ...................................................... 4 9 
Cli nic al M o nit ori n g ........................................................................................................... ..................................................... 4 9 
Q u alit y Ass ur a nc e a n d Q u alit y C o ntr ol ......................................................................................... ........................................ 5 0 
D at a C oll ecti o n a n d M a n a g e m e nt R es p o n si biliti es .............................................................................................................. 5 0 
St u d y R ec or ds R et e nti o n ....................................................................................................... ................................................ 5 0 
R ef er e nc es .................................................................................................................... ........................................................ 5 1 
 
St at e m e nt of C o m pli a nc e  
T h e tri al will b e c arri e d o ut i n acc or d a n c e wit h I nt er n ati o n al C o nf er e nc e o n H ar m o niz ati o n G o o d Cli nic al Pr actic e (I C H 
G C P) a n d t h e f oll o wi n g:  
 
• 
U nit e d St at es ( U S) C o d e of F e d er al R e g ul ati o ns ( C F R) a p plic a bl e t o cli nic al st u di es ( 4 5 C F R P art 4 6, 2 1 C F R 
P art 5 0, 2 1 C F R P art 5 6, 2 1 C F R P art 3 1 2, a n d/ or 2 1 C F R P art 8 1 2)  
 
U ni v ersit y of Mi a mi i n v esti g at ors a n d cli nic al tri al sit e  st aff w h o ar e r es p o nsi bl e f or t h e c o n d uct, m a n a g e m e nt, or 
o v ersi g ht of t his cli nic al tri al h a v e c o m pl et e d H u m a n S u bj ects Pr ot ecti o n a n d I C H G C P Tr ai ni n g. 
 
T h e pr ot oc ol, i nf or m e d c o ns e nt f or m(s), r ecr uit m e nt m at eri als, a n d all p artici pa nt m at eri als will b e s u b mitt e d t o t h e 
I nstit uti o n al R e vi e w B o ar d (I R B) a n d r el at e d a ncill ar y c o m mitt e es f or r e vi e w a n d a p pr o v al.  A p pr o v al of b ot h t h e 
pr ot oc ol a n d t h e c o ns e nt f or m m ust b e o bt ai n e d b ef or e a n y p artici p a nt is e nr oll e d.  A n y a m e n d m e nt t o t h e pr ot oc ol will 
r e q uir e r e vi e w a n d a p pr o v al b y t h e I R B b ef or e t h e c h a n g es ar e i m pl e m e nt e d t o t h e st u d y.  I n a d diti o n, all c h a n g es t o t h e 
c o ns e nt f or m will b e I R B- a p pr o v e d; a d et er mi n ati o n will b e m a d e r e g ar di n g w h et h er a n e w c o ns e nt n e e ds t o b e 
o bt ai n e d fr o m p artici p a nts w h o pr o vi d e d c o ns e n t, usi n g a pr e vi o usl y a p pr o v e d c o ns e nt f or m. 
 

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C o nfi de ntial
  
Sy n o psis  
Titl e: 
U m bilic al C or d- d eri v e d M es e nc h y m al St e m C ells f or C O VI D- 1 9 P ati e nts 
wit h Ac ut e R es pir at or y Distr ess S y n dr o m e ( A R D S) 
 
St u d y D escri pti o n: 
T his is a r a n d o miz e d, c o ntr oll e d, d o u bl e bli n d m ulti-c e nt er tri al t o e v al u at e 
pri m aril y s af et y a n d s ec o n d ar y ex pl or at or y effic ac y e n d p oi nts of all o g e n eic 
U C- M S C i n C O VI D- 1 9 p ati e nts wit h A R D S, wit h t w o gr o u ps: tr e at m e nt 
gr o u p ( n = 1 2) w h er e t h e s u bj ects will b e tr e at e d wit h t w o i nf usi o ns of U C-
M S C I n v esti g ati o n al Pr o d uct ( 1 0 0x 1 0 6 c ells/i nf usi o n, r es us p e n d e d i n 
Pl as m a-L yt e s u p pl e m e nt e d wit h 1 % H u m a n S er u m Al b u mi n ( H S A) a n d 7 0 
U/ K g u nfr acti o n at e d H e p ari n, d eli v er e d I V) a n d st a n d ar d of c ar e. a n d 
c o ntr ol gr o u p ( n = 1 2) w h er e s u bj ects will r ec ei v e t w o i nf usi o ns of v e hicl e 
( Pl as m a-L yt e s u p pl e m e nt e d wit h 1 0 % H S A a n d 7 0 U/ K g u nfr acti o n at e d 
H e p ari n, d eli v er e d I V) a n d st a n d ar d of c ar e. 
 
 
O bj ecti v es: 
 
T h e pr o p os e d st u d y will ass ess pri m aril y s af et y a n d s ec o n d ar y ex pl or at or y 
effic ac y e n d p oi nts of all o g e n eic U C- M S Cs.  
 
 
 
T h e pri m ar y o bj ecti v e  of t h e tri al is t o ass ess tr e at m e nt- ass oci at e d 
a d v ers e e v e nts ( A Es) a n d s eri o us a d v ers e e v e nts ( S A Es) at 9 0 d a ys p ost 
first i nf usi o n. 
 
T h e s ec o n d ar y o bj ecti v es ar e t o i n v esti g at e effic ac y wit h e n d p oi nts 
d efi n e d b y:  
 
1) Cli nic al o utc o m es i ncl u di n g s ur vi v al v e ntil at or-fr e e d a ys, ox y g e n ati o n 
i n d ex ( OI), v e ntil at or p ar a m et ers ( e. g., p ositi v e e n d- ex pir at or y pr ess ur e 
[ P E E P], pl at e a u pr ess ur e [ P pl at], c o m pli a nc e), a n d S e q u e nti al Or g a n 
F ail ur e Ass ess m e nt ( S O F A). 
 
2) L a b or at or y t ests, i ncl u di n g c o m pl et e bl o o d c o u nt wit h diff er e nti al, 
c o m pr e h e nsi v e m et a b olic p a n el, i nfl a m m at or y m ar k ers s uc h as C-r e acti v e 
pr ot ei n ( C R P), D- di m er, a n d ar ac hi d o nic aci d ( A A) t o eic os a p e nt a e n oic aci d 
( E P A) r ati o ( A A/ E P A r ati o), 2 5- O H vit a mi n D l e v els, a n d all o a nti b o di es 
( P R A). 
  
3) M ec h a nistic st u di es m a y i ncl u d e: 
(i) A n al ysis of i m m u n e c ell s u b- p o p ul ati o ns: p eri p h er al bl o o d m o n o n ucl e ar 
c ell ( P B M C) ass ess m e nt of T c ell p o p ul ati o ns, i ncl u di n g o v er acti v at e d 
c yt o ki n e s ecr eti n g C X C R 3 + C D 4 + T c ells, C X C R 3 + C D 8 + T c ells, C X C R 3 + N K 
c ells, C D 1 4 + C D 1 1c + C D 1 1 b mi d r e g ul ator y D C c ell p o p ul ati o n;(ii) 
Ass ess m e nt of 4 0 c yt o ki n es, c h e m o ki n es a n d gr o wt h f act ors f o u n d i n 
pl as m a, usi n g m ulti pl ex ELI S A. (iii)  Ass ess m e nt of S 1 P a n d s P D-L 1 i n 
pl as m a.  
 
 
E n d p oi nts: 
Pri m ar y E n d p oi nt  of t his tri al is t o est a blis h s af et y, as d efi n e d b y t h e 
occ urr e nc e of Pr e-s p ecifi e d I nf usi o n Ass oci at e d A d v ers e e v e nts aft er 
i nf usi o n. A n y of t h e f oll o wi n g occ urri n g wit hi n 6 h p ost e ac h i nf usi o n: 
1. A n i ncr e as e i n v as o pr ess or d os e gr e at er t h a n or e q u al t o t h e f oll o wi n g: 

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C o nfi de ntial
  
•  
N or e pi n e p hri n e: 1 0 μ g p er mi n  
•  
P h e n yl e p hri n e: 1 0 0 μ g p er mi n  
•  
D o p a mi n e: 1 0 μ g/ k g p er mi n  
•  
E pi n e p hri n e: 1 0 μ g p er mi n  
2. I n p ati e nts r ec ei vi n g m ec h a nic al v entil ati o n: w ors e ni n g h y p ox e mi a, as 
ass ess e d b y a r e q uir e m e nt f or a n i ncr e as e of P E E P b y 5 c m H 2 O o v er 
b as eli n e, or r e q uir e m e nt of a p erc e nt a g e i ncr e as e i n Fi O 2 of > 2 0 % fr o m 
b as eli n e  .  
3. I n p ati e nts r ec ei vi n g hi g h fl o w ox y g e n t h er a p y: w ors e ni n g h y p ox e mi a, as 
i n dic at e d b y r e q uir e m e nt of i nt u b ati o n a n d m ec h a nic al v e ntil ati o n. 
4. N e w c ar di ac arr h yt h mi a  r e q uiri n g c ar di o v ersi o n 
5. N e w v e ntric ul ar t ac h yc ar di a, v e nt ric ul ar fi brill ati o n, or as yst ol e 
6. A cli nic al sc e n ari o c o nsist e nt wit h tr a nsf usi o n i nc o m p ati bilit y or 
tr a nsf usi o n-r el at e d i nf ecti o n 
7. C ar di ac arr est or d e at h wit hi n 2 4 h p ost i nf usi o n 
 
I nci d e nc e of S e v er e A d v ers e E v e nts ( S A Es) [ Ti m e Fr a m e: I n v esti g at ors will 
c o n d uct d ail y ass ess m e nts f or t h e pr es e nc e of a n y a d v ers e e v e nts ( A E) 
fr o m e nr oll m e nt t hr o u g h h os pit al disc h ar g e, a n d t h e n vi a T el e h e alt h or 
cli nic al sit e visits].  
 
S ec o n d ar y E n d p oi nts  i ncl u d es ex pl or at or y effic ac y d efi n e d b y 
1. Cli nic al o utc o m es t h at i ncl u d e 
•  
S ur vi v al at d a y 2 8  
•  
S ur vi v al at d a y 6 0  
•  
Ti m e t o h os pit al disc h ar g e  
•  
V e ntil at or-fr e e d a ys  
•  
Ox y g e n ati o n i n dic es: 
o  I n p ati e nts r ec ei vi n g Hi g h Fl o w Ox y g e n t h er a p y: R O X i n d ex 
d efi n e d as R O X = ( S p O 2/ Fi O 2)/r es pir at or y r at e ( R R) 
o  I n p ati e nts o n m ec h a nic al v e ntil ati o n: Ox y g e n ati o n I n d ex 
( OI), d efi n e d as OI = ( Fi O 2 x M P A W)/ P a O 2; w h er e Fi O 2 = 
fr acti o n of i ns pir e d O 2; M P A W = M e a n air w a y pr ess ur e 
( v e ntil at or); a n d P a O 2 = p arti al pr ess ur e of ox y g e n i n 
art eri al bl o o d 
•  
Dri vi n g Pr ess ur e ( P pl at – P E E P) if  a p plic a bl e a n d a v ail a bl e i n t h e 
el ectr o nic m e dic al r ec or d c h arts  
•  
S O F A ( S e q u e nti al Or g a n F ail ur e Ass ess m e nt)  
•  
S m ell I d e ntific ati o n T est ( SI T) or olf act or y t esti n g  
 
2. L a b or at or y t esti n g:  
•  
C o m pl et e Bl o o d C o u nt ( C B C) wit h diff er e nti al  
•  
M et a b olic P a n el ( M P)  
•  
C-r e acti v e pr ot ei n  
•  
A A/ E P A r ati o  
•  
D- di m er  
•  
2 5- O H Vit a mi n D l e v els  
•  
All o a nti b o di es ( P a n el R e ac ti v e A nti b o di es [ P R A]) 
•  
Vir al L o a d b y S A R S- C o V- 2 R T- P C R  
S er ol o g y t esti n g f or S A R S- C o V- 2 I g G/I g M  

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C o nfi de ntial
  
 
3. M ec h a nistic st u di es m a y i ncl u d e 
•  
M ulti pl ex ELI S A ass essi n g of pl as m a I nfl a m m at or y p a n el ( # 4 0) of 
c yt o ki n es, c h e m o ki n es a n d gr o wt h f act ors    
•  
ELI S A ass ess m e nt of pl as m a l e v els of S 1 P a n d s P D-L 1  
•  
P B M C ass ess m e nt of T c ell p o p ul ati o ns a, i ncl u di n g:  
o  O v er acti v at e d c yt o ki n e-s ecr eti n g C X C R 3 + C D 4 + T c ells  
o  C X C R 3 + C D 8 + T c ells  
o  C X C R 3 + N K c ells  
o  C D 1 4 + C D 1 1c + C D 1 1 b mi d r e g ul at or y D C c ell p o p ul ati o n  
o  C D 4 + C D 2 5 + F O X P 3 + Tr e gs  
 
 
St u d y P o p ul ati o n: 
I ncl usi o n Crit eri a 
P ati e nts ≥ 1 8 y e ars ol d di a g n os e d wit h C O VI D- 1 9 ( as e v al u at e d b y P C R t est 
c o nfir mi n g i nf ecti o n wit h S A R S- C o V- 2) w ill b e eli gi bl e f or i ncl usi o n if t h e y 
m e et all of t h e b el o w crit eri a. I ncl usi o n crit eri a m ust all b e pr es e nt wit hi n 
a 2 4- h o ur ti m e p eri o d at t h e ti m e of e nr oll m e nt: 
1.  P ati e nt c urr e ntl y h os pit aliz e d 
2.  A g e d ≥ 1 8 y e ars 
3.  Willi n g a n d a bl e t o pr o vi d e writt e n i nf or m e d c o ns e nt, or wit h a 
l e g al r e pr es e nt ati v e w h o c a n pr o vi d e i nf or m e d c o ns e nt 
4.  P eri p h er al c a pill ar y ox y g e n s at ur ati o n ( S p O 2) ≤ 9 4 % at r o o m air, or 
r e q uiri n g s u p pl e m e nt al ox y g e n at scr e e ni n g 
5.  P a O 2/ Fi O2 r ati o < 3 0 0 m m H g 
6.  Bil at er al i nfiltr at es o n fr o nt al c h est r a di o gr a p h or bil at er al gr o u n d 
gl ass o p aciti es o n a c h est C T sc a n 
 
Excl usi o n Crit eri a 
Excl usi o n Crit eri a 
1.  P a O 2/ Fi O2 ≥ 3 0 0 at t h e ti m e of e nr oll m e nt 
2.  A pr e vi o us M S C i nf usi o n n ot r el at e d t o t his tri al 
3.  Hist or y of P ul m o n ar y H y p ert e nsi o n ( W H O Cl ass III/I V) 
4.  Cli nic al e vi d e nc e of l eft atri al h y p ert e nsi o n or d ec o m p e ns at e d l eft 
h e art f ail ur e. 
5.  Pr e g n a nt or l act ati n g p ati e nt 
6.  U nst a bl e arr h yt h mi a  
7.  P ati e nts wit h pr e vi o us l u n g tr a ns pl a nt 
8.  P ati e nts c urr e ntl y r ec ei vi n g c hr o nic di al ysis  
9.  P ati e nts
 c urr e ntl y
 r ec ei vi n g
 Extr ac or p or e al
 M e m br a n e
 
Ox y g e n ati o n ( E C M O) 
1 0.  E vi d e nc e  of  a n y  acti v e  m ali g n a nc y  ( exc e pt  n o n- m el a n o m a  s ki n  
c a nc er) 
1 1.  A n y ot h er irr e v ersi bl e dis e as e or c o n diti o n f or w hic h 6- m o nt h 
m ort alit y is esti m at e d t o b e gr e at er t h a n 5 0 % 
1 2.  M o d er at e t o s e v er e li v er dis e as e ( A S T a n d AL T > 5 X UL N)  
1 3.  S e v er e c hr o nic r es pir at or y dis e as e wit h a P a C O 2 > 5 0 m m H g or t h e 

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C o nfi de ntial
  
us e of h o m e ox y g e n 
1 4.  B as eli n e Q T pr ol o n g ati o n 
1 5.  M ori b u n d p ati e nt n ot ex p ect e d t o s ur vi v e > 2 4 h o urs  
 
Pl e as e n ot e t h at di p h e n h y dr a mi n e, h y dr ox yc hl or o q ui n e, a n d azit hr o m yci n 
all pr ol o n g t h e c ar di ac Q T i nt er v al , i ncr e asi n g ris k of f at al c ar di ac 
arr h yt h mi a. T h er ef or e, i n s e v er el y-ill s u bj ects r ec ei vi n g m ulti pl e dr u gs t h at 
pr ol o n g Q T i nt er v als, t h e PI will c o nsi d er c as e- b y-c as e a dj u dic ati o n f or 
b e n efit-ris k r ati o a n d cl os e c ar di o v asc ul ar m o nit ori n g. 
 
 
P h as e: 
P h as e I/II a acr oss fi v e ( 5) sit es, l o c all y ( Mi a mi) a n d r e m ot el y acr oss t h e 
U S A 
 
 
D escri pti o n of 
Sit es/ F aciliti es E nr olli n g  
P artici p a nts: 
T his m ulti-c e nt er tri al will b e c o n d uct e d at fi v e ( 5) sit es, i ncl u di n g t h e 
U ni v ersit y of Mi a mi H e alt h S yst e m / J ac ks o n H e alt h S yst e m a n d ot h er 
c e nt ers acr oss t h e U S A.  
 
  
 
D escri pti o n of St u d y 
I nt er v e nti o n: 
T h e tri al h as t w o gr o u ps, e ac h wit h 1 2 s u bj ects ( n = 2 4). All eli gi bl e s u bj ects 
will b e r a n d o miz e d t o eit h er t h e tr e a t m e nt gr o u p or c o ntr ol gr o u p, a n d 
r a n d o miz ati o n will b e str atifi e d b y A R D S s e v erit y. 
 
A R D S s e v erit y will b e d efi n e d b y a r ati o of t h e p arti al pr ess ur e of art eri al 
ox y g e n t o t h e fr acti o n of  i ns pir e d ox y g e n, wit h mil d-t o- m o d er at e A R D S  
d efi n e d as a r ati o > 1 5 0 m m H g a n d m o d er at e-t o-s ev er e A R D S  d efi n e d as a 
r ati o < 1 5 0 m m H g. 
P ati e nts i n t h e tr e at m e n t gr o u p will b e tr e at e d wit h t w o i nf usi o ns of U C-
M S C I n v esti g ati o n al Pr o d uct ( 1 0 0x 1 0
6 c ells/i nf usi o n, r es us p e n d e d i n 
Pl as m a-L yt e s u p pl e m e nt e d wit h 1 0 % H u m a n S er u m Al b u mi n ( H S A) a n d 7 0 
U/ K g u nfr acti o n at e d H e p ari n, d eli v er e d I V) a n d will r ec ei v e st a n d ar d of 
c ar e.  
P ati e nts i n t h e c o ntr ol gr o u p will r e c ei v e t w o i nf usi o ns of v e hicl e ( Pl as m a-
L yt e s u p pl e m e nt e d wit h 1 0 % H S A a n d 7 0 U/ K g u nfr acti o n at e d H e p ari n, 
d eli v er e d I V) a n d st a n d ar d of c ar e. 
 
S u bj ects will b e f oll o w e d fr o m e nr oll m e nt t o st u d y d a y 9 0.  
 
I n b ot h gr o u ps, t h e first i nf usi o n will b e a d mi nist er e d wit hi n 2 4 ± 6 h o urs 
f oll o wi n g st u d y e nr oll m e nt. All s u bj ects will b e e v al u at e d at b as eli n e a n d 
f oll o w e d st arti n g fr o m t h e ti m e of i nf usi o n. S u bj ects will b e e v al u at e d at 
2 4 ± 6 h p ost-first i nf usi o n a n d d ail y f or t h e first 6 d a ys.  A s ec o n d i nf usi o n 
will b e a d mi nist er e d at 7 2 ± 6 h aft er t h e first i nf usi o n. I n a d diti o n, s u bj ects 
e nr oll e d i n t h e tri al will b e f oll o w e d f or 9 0 d a ys aft er t h e i niti al i nf usi o n, 
acc or di n g t o t h e sc h e d ul e of ass ess m e nt.  W e will us e c o nc urr e nt p ar all el 
c o ntr ols t o esti m at e diff er e nc es i n A Es, S A Es, a n d cli nic al i n dic at ors.  
  
T o c o ntr ol f or v ari a bilit y i n st u d y t h er a p y, st u d y s u bj ects will b e tr e at e d 

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C o nfi de ntial
  
wit h U C- M S Cs d eri v e d fr o m a si n gl e m ast er c ell b a n k ( M C B) (si n gl e U C 
s o urc e). T w o b atc h es of U C- M S C fi n al pr o d uct will b e n ec ess ar y t o s atisf y 
d os e r e q uir e m e nts of t h e st u d y.  
 
 
Ai m 1 will ass ess s af et y of U C- M S C st u d y t h er a p y, Ai m 2 will ex pl or e 
effic ac y of t h e U C- M S C tr e at m e nt vi a cl i nic al p ar a m et ers, l a b or at or y t ests, 
a n d m ec h a nistic st u di es t o a d dr ess U C- M S C i m m u n o m o d ul at or y a n d 
tiss u e r e p air/r e g e n er ati o n pr o p erti es.  
 
St u d y D ur ati o n: 
1 y e ar ( 1 2 m o nt hs) 
 
 
P artici p a nt D ur ati o n: 
9 0 d a ys ( 3 m o nt hs)  
 
A bstr act 
T h e c or o n a vir us S A R S- C o V- 2 is c a us e of a gl o b al p a n d e mic of a p n e u m o ni a-li k e dis e as e t er m e d C or o n a vir us Dis e as e 
2 0 1 9 ( C O VI D- 1 9), f or w hic h n o tr e at m e nt ex ists.  H y p er-i nfl a m m at or y r es p o ns es i n p ati e nts wit h s e v er e dis e as e c a us e 
d e at h, l ar g el y t hr o u g h Ac ut e R es pir at or y Distr ess S y n dr o m e ( A R D S).  M es e nc h y m a l st e m c ells ( M S C) h a v e b e e n s h o w n 
s af e, wit h si g n als of effic ac y i n r e v ersi n g A R D S c a us e d b y C O VI D- 1 9.  M S C d eri v e d fr o m t h e U m bilic al C or d ( U C- M S C) 
p oss ess s u p eri or p ot e nc y c o m p ar e d t o M S C fr o m ot h er s o urc es,  i n a d diti o n t o ec o n o mic a n d pr actic al b e n efits.  O ur 
gr o u p h as s ucc essf ull y us e d U C- M S C i n a v ari et y of i nfl a m m at o r y c o n diti o ns i n pr ecli nic al a n d cli nic al tri als. W e ar e 
pr o p osi n g a m ulti- c e nt er, c o ntr oll e d, r a n d o miz e d cli nic al st u d y t o e v al u at e s af e t y a n d effic ac y of U C- M S C i ntr a v e n o us 
(I V) a d mi nistr ati o n i n p ati e nts wit h C O VI D- 1 9.  S u bj ects i n t h e tr e at m e nt gr o u p will b e tr e at e d wit h t w o d os es of U C-
M S C ( 1 0 0 x 1 0
6 c ells). T h e first d os e will b e i nf us e d wit hi n 2 4 h o urs f oll o wi n g st u d y e nr oll m e nt. A s ec o n d d os e will b e 
a d mi nist er e d 7 2 +/- 6 h o urs aft er t h e first i nf usi o n. S u bj ect i n  t h e c o ntr ol gr o u p will r ec ei v e i nf usi o n of v e hicl e ( Pl as m a-
L yt e s u p pl e m e nt e d wit h 1 0 % H S A a n d 7 0 U/ K g u nfr acti o n at e d H e p ari n, d eli v er e d I V) f oll o wi n g t h e s a m e ti m eli n e.   
S u bj ects will b e e v al u at e d d ail y d uri n g t h e first 6 d a ys, t h e n at 1 4, 2 8, 6 0, a n d 9 0 d ays f oll o wi n g e nr oll m e nt (s e e 
Sc h e d ul e of Ass ess m e nt f or ti m e wi n d o w d et ails). S af et y will b e d et er mi n e d b y a d v ers e e v e nts ( A Es) a n d s eri o us a d v ers e 
e v e nts  ( S A Es)  d uri n g  t h e  f oll o w- u p  p eri o d.   Effic ac y  will  b e  d efi n e d  b y  cli nic al  o utc o m es,  as  w ell  as  a  v ari et y  of  
p ul m o n ar y, bi oc h e mic al a n d i m m u n ol o gic al t ests.  S ucc ess of t h e c urr e nt st u d y will pr o vi d e a fr a m e w or k f or l ar g er 
c o ntr oll e d, r a n d o miz e d cli nic al tri als a n d a m e a ns of acc el er ati n g a p ossi bl e s ol uti o n f or t his ur g e nt b ut u n m et m e dic al 
n e e d.   
 
 
P u blic H e alt h R el ev a nc e St at e m e nt 
C or o n a vir us dis e as e 2 0 1 9 ( C O VI D- 2 0 1 9) is c a us e d b y a hi g hl y c o nt a gi o us c or o n a vir us, S A R S- C o V- 2; it h as r a pi dl y s pr e a d 
ar o u n d t h e w orl d si nc e its first d et ecti o n i n H u b ei Pr o vi nc e , C hi n a, i n D ec e m b er of 2 0 1 9. T h e first p ati e nts at t h e 
e pic e nt er of t h e o ut br e a k h a d a li n k t o a l ar g e s e af o o d a n d li v e a ni m al m ar k et, s u g g esti n g a n a ni m al-t o- p ers o n s pr e a d. 
L at er w a v es of p ati e nts t esti n g p ositi v e f or C O VI D- 1 9 h a d n o  ass oci ati o n wit h t h e ori gi n al f o o d m ar k et, s u g g esti n g a 
p ers o n-t o- p ers o n s pr e a d of t h e dis e as e. It is t his m o d e of dis e as e tr a ns missi o n t h at h as c a us e d t h e wi d e a n d r a pi d 
s pr e a d of t his dis e as e ar o u n d t h e w orl d, a n d is n o w d ecl ar e d a p a n d e mic. S e v er e/critic al f or m  of t h e dis e as e d e v el o ps i n 
a p pr oxi m at el y 1 9 % of p ati e nts t esti n g p ositi v e f or S A R S- C o V- 2. A m o n g t h es e, a m ort alit y r at e of 4 6- 4 9 % h as b e e n 
o bs er v e d.  I n  t h e  a bs e nc e  of  a n  a p pr o v e d  v acci n e,  r el yi n g  s ol el y  o n  s u p p orti v e  c ar e  t h at  c o nsists  o n  m ec h a nic al  
v e ntil ati o n i n s u p p ort of vit al or g a n f u ncti o ns, d e v el o p m e n t of n o v el t h er a pi es ai m e d at tr e at m e nt of p ati e nts wit h 
s e v er e  m a nif est ati o ns  of  C O VI D- 1 9  dis e as e,  i. e.  ALI  a n d  A R D S,  w h o  r a pi dl y  pr o gr ess  t o  or g a n  f ail ur e  is  of  critic al  
i m p ort a nc e.  D u e  t o  t h eir  i m m u n o m o d ul at or y  a n d  a nti-i nfl a m m at or y  pr o p erti es,  U C- M S C  t h er a p y  h as  b e e n  s h o w n  
effic aci o us  i n  a  n u m b er  of  a ut oi m m u n e  c o n diti o ns,  T y p e  1  Di a b et es,  or g a n  tr a ns pl a nt ati o n,  c ar di ac  i ns uffici e nc y,  

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p ati e nts wit h Alz h ei m er’s dis e as e, a n d r ec e ntl y p ati e nts wit h  s e v er e f or ms of C O VI D- 1 9 dis eas e, alt h o u g h l ar g er st u di es 
ar e n ec ess ar y. D e v el o p m e nt of cli nic al gr a d e M S C t h er a pi es t o  tr e at t h e dis e as e c a us e d b y S A R S- C o V- 2 is of p ar a m o u nt 
i m p ort a nc e, t o i m pr o v e gl o b al p u blic h e alt h a n d c urt ail t h e c urr e nt C O VI D- 1 9 e pi d e mic. 
 
Ex ec utiv e S u m m ary 
 
Pr o bl e m : A hi g hl y c o nt a gi o us c or o n a vir us, S A R S- C o V- 2 ( pr e vio usl y k n o w n as 2 0 1 9- n C o V), is s pr e a di n g r a pi dl y ar o u n d 
t h e w orl d, c a usi n g a s h ar p ris e of a p n e u m o ni a-li k e dis e ase t er m e d C or o n a vir us Dis e as e 2 0 1 9 ( C O VI D- 1 9) ( 1, 2). C O VI D-
1 9 pr es e nts a hi g h m ort alit y r at e, esti m at e d at 3. 4 % b y t h e W o rl d H e alt h Or g a niz ati o n ( 3). T h e r a pi d s pr e a d of t h e vir us 
( esti m at e d r e pr o d ucti v e n u m b er R0 2. 2 – 3. 6 ( 4, 5)) is c a usi n g a si g nific a nt s ur g e of p ati e nts r e q uiri n g i nt e nsi v e c ar e. 
M or e t h a n 1 o ut of 4 h os pit aliz e d C O VI D- 1 9 p ati e nts h a v e r e q uir e d a d missi o n t o a n I nt e nsi v e C ar e U nit (I C U) f or 
r es pir at or y s u p p ort, a n d a l ar g e pr o p orti o n of t h es e I C U- C OVI D- 1 9 p ati e nts, b et w e e n 1 7 % a n d 4 6 %, h a v e di e d ( 6- 1 0).  
 
A c o m m o n o bs er v ati o n a m o n g p ati e nts wit h s e v er e C O VI D- 1 9 i nf ecti o n is a h y p er-i nfl a m m at or y r es p o ns e l oc aliz e d t o 
t h e l o w er r es pir at or y tr act ( 1 1- 1 3). T his i nfl a m m ati o n, ass oci at e d wit h d ys p n e a a n d h y p ox e mi a, i n s o m e c as es e v ol v es 
i nt o  exc essi v e  i m m u n e  r es p o ns e  wit h  c yt o ki n e  st or m,  d et er mi ni n g  pr o gr essi o n  t o  Ac ut e  L u n g  I nj ur y  ( ALI),  Ac ut e  
R es pir at or y Distr ess S y n dr o m e ( A R D S), or g a n f ail ur e, a n d d e at h ( 2 , 1 0). Dr ac o ni a n m e as ur es h a v e b e e n p ut i n pl ac e i n a n 
att e m pt t o c urt ail t h e i m p act of t h e C O VI D- 1 9 e pi d e mic o n p o p ul ati o n h e alt h a n d h e alt hc ar e s yst e ms. H o w e v er, W H O 
h as n o w cl assifi e d C O VI D- 1 9 a p a n d e mic ( 3).  
 
At t h e pr es e nt ti m e, t h er e is n eit h er a v acci n e n or s p ecific a nti vir al tr e at m e nts f or s eri o usl y ill p ati e nts i nf ect e d wit h 
C O VI D- 1 9. Cr uci all y, n o o pti o ns ar e a v ail a bl e f or t h os e p ati e n ts wit h r a pi dl y pr o gr essi n g A R D S e v ol vi n g t o or g a n f ail ur e. 
Alt h o u g h s u p p orti v e c ar e is pr o vi d e d w h e n e v er p ossi bl e, i ncl u di n g m ec h a nic al v e ntil ati o n a n d s u p p ort of vit al or g a n 
f u ncti o ns, it is i ns uffici e nt i n m ost s e v er e c as es. T h er ef or e, t h er e is a n ur g e nt n e e d f or n o v el t h er a pi es t h at c a n d a m p e n 
t h e  exc essi v e  i nfl a m m at or y  r es p o ns e  i n t h e  l u n gs,  ass oci at e d  wit h  t h e  i m m u n o p at h ol o gic al  c yt o ki n e  st or m,  a n d  
acc el er at e t h e r e g e n er ati o n of f u ncti o n al l u n g tiss u e i n C O VI D- 1 9 p ati e nts.  
 
R es e arc h Hy p ot h esis : T w o d os es of i ntr a v e n o usl y a d mi nist er e d u m bilical c or d m es e nc h y m al st e m c ells ( U C- M S C, 1 0 0 
x 1 0 6 c ells/ d os e) s e p ar at e d b y a 7 2 + 6 h o ur i nt er v al will b e s af e a n d r e d uc e p at h ol o g y i n p ati e nts wit h C O VI D- 1 9 i n d uc e d 
A R D S. 
 
R ati o n al e :  M es e nc h y m al St e m C ells ( M S Cs) are p ot e nt i m m u n o m o d ul at or y c ells t h at r ec o g niz e sit es of i nj ur y, li mit 
eff ect or T c ell r e acti o ns, a n d sti m ul at e r e g ul at or y c ell p o p ul ati o ns ( i. e., T-r e gs) vi a gr o wt h f act ors, c yt o ki n es, a n d ot h er 
m e di at ors. Si m ult a n e o usl y, M S Cs als o sti m ul at e l oc al tiss u e r e g e n er ati o n vi a p ar acri n e eff ects i n d uci n g a n gi o g e nic, a nti-
fi br otic a n d r e m o d eli n g r es p o ns es( 1 4). C o ns e q u e ntl y, M S Cs- b as e d t h er a p y r e pr es e nts a vi a bl e tr e at m e nt o pti o n f or 
a ut oi m m u n e c o n diti o ns a n d ot h er i nfl a m m at or y dis or d ers ( 1 5- 2 0), yi el di n g b e n efici al eff ects i n m o d els of a ut oi m m u n e 
T y p e 1 Di a b et es ( 2 1- 2 7), S yst e mic L u p us Er yt h e m at os us, A ut oi m m u n e E nc e p h al o m y elitis ( 2 8), M ulti pl e Scl er osis ( 2 9, 
3 0), c ar di ac i ns uffici e nc y ( 3 1, 3 2), a n d or g a n tr a ns pl a nt ati o n ( 3 3). M S Cs h a v e b e e n r e p ort e d t o i n hi bit i nfl a m m ati o n a n d 
fi br osis i n t h e l u n gs ( 3 4- 3 7) a n d h a v e b e e n r ec e ntl y s u g g est e d as us ef ul t o tr e at p ati e nts wit h s e v er e C O VI D- 1 9 b as e d o n 
t h eir eff ects pr e v e nti n g or att e n u ati n g t h e i m m u n o p at h o g e nic c yt o ki n e st or m ( 3 8- 4 1). M S Cs c a n b e e asil y d eri v e d i n 
l ar g e n u m b ers fr o m t h e U m bilic al C or d ( U C) a n d c a n b e r a pi dl y ex p a n d e d i nt o cli nic all y-r el e v a nt n u m b ers.  
A p o p ul ati o n of U C- M S Cs of i nt er est w as d e m o nstr at e d t o m a i nt ai n its ex p a nsi o n c a p acit y o v er 9 0 p o p ul ati o n d o u bli n gs 
wit h o ut c ell s e n esc e nc e, w hil e m ai nt ai ni n g M S C c h ar act eristics a n d f u ncti o ns ( 4 2) . U C- M S C h a v e d e m o nstr at e d s af et y 
a n d effic ac y i n cli nic al tri als, a n d h a v e  b e e n s af el y a d mi nist er e d acr oss hist oc o mp ati bilit y b arri ers. U C- M S Cs pr oc ess e d at 
o ur f acilit y h a v e b e e n r ec e ntl y i ntr o d uc e d i ntr a v e n o usl y i n p ati e nts wit h Alz h ei m er`s Dis e as e ( 4 3), a n d h a v e b e e n 
a p pr o v e d f or t esti n g i n p ati e nts wit h T y p e 1 Di a b et es ( T 1 D).  
 

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I m p ort a nc e of t h e R es e arc h: T h e pr o p os e d st u d y will pr o vi d e t h e first q u a ntit ati v e a n al ysis of s af et y a n d effic ac y 
usi n g w h at a p p e ars t o b e t h e m ost p ot e nt a n d pr actic al M S C t y p e t o h a v e e nt er e d t h e cli nic.  S ucc ess of t his tri al will 
pr o vi d e b asis f or pi v ot al tri als.  
 
 
O bj ectiv es  
 
T h e pr o p os e d st u d y will ass ess pri m aril y s af et y a n d s ec o n d ar y ex pl or at or y effic ac y e n d p oi nts of all o g e n eic U C- M S C i n a 
m ulti-c e nt er, r a n d o miz e d c o ntr oll e d tri al ( R C T) i n s u bj ects wit h s e v er e c as es of C O VI D- 1 9. T h e tr e at m e nt gr o u p will 
i ncl u d e  1 2 s u bj ects w h o will r ec ei v e i nf usi o ns of U C- M S C i n v esti g ati o n al pr o d uct (I P) a n d st a n d ar d of c ar e. T h e 1 2 
s u bj ects i n t h e c o ntr ol gr o u p will r ec ei v e i nf usio ns of v e hicl e s ol uti o n a n d st a n d ar d of c ar e.  
 
Pri m ary o bj ectiv e 
T h e pri m ar y o bj ecti v e  of t h e tri al is t o ass ess tr e at m e nt- ass oci at e d a d v ers e e v e nts ( A Es) a n d s eri o us a d v ers e e v e nts 
( S A Es) at 9 0 d a ys p ost i nf usi o n.  
 
S ec o n d ary o bj ectiv e 
T h e s ec o n d ar y o bj ecti v es ar e t o i n v esti g at e e arl y effic ac y e n d p oi nts, i ncl u di n g:  
a) Cli nic al o utc o m es  i ncl u di n g s ur vi v al v e ntil at or-fr e e d a ys, ox y g e n ati on i n d ex ( OI), v e ntil at or p ar a m et ers ( e. g., P E E P, 
P pl at, c o m pli a nc e), S e q u e nti al Or g a n F ail ur e Ass ess m e nt ( S O F A). 
b) L a b or at ory t ests,  i ncl u di n g c o m pl et e bl o o d c o u nt wit h diff er e nti al, c o m pl et e m et a b olic p a n el, i nfl a m m at or y m ar k ers 
s uc h as C- R e acti v e Pr ot ei n a n d A A/ E P A r ati o, 2 5-O H vit a mi n D l e v els, a n d all o a nti b o di es ( P R A)  
c) M ec h a nistic st u di es m ay i ncl u d e  
(i) A n al ysis of i m m u n e c ell s u b- p o p ul ati o ns:  p eri p h er a l bl o o d m o n o n ucl e ar c ell ( P B M C) ass ess m e nt of T c ell 
p o p ul ati o ns, i ncl u di n g o v er acti v at e d c yt o ki n e-s ecr eti n g C X C R 3 + C D 4 + T c e lls, C X C R 3 + C D 8 + T c ells, C X C R 3 + N K 
c ells, C D 1 4 + C D 1 1c + C D 1 1 b mi d r e g ul at or y D C c ell p o p ul ati o n;  
(ii) Ass ess m e nt of i nfl a m m at or y c yt o ki n es,  c h e m o ki n es a n d gr o wt h f act ors f o u n d i n pl as m a usi n g m ulti pl ex ELI S A 
ass a ys, as w ell as S 1 P a n d s P D-L 1.  
 
S p ecific Ai ms  
D at a fr o m s m all a ni m al, pr ecli nic al a ni m al m o d els a n d a n u m b er of cli nic al tri als h a v e cl e arl y s h o w n t h at M S C p oss ess 
i m m u n o m o d ul at or y  a n d  a nti-i nfl a m m at or y  pr o p erti es( 1 4).  U C- M S C  t h er a p y,  a d mi nist er e d  I V  h as  b e e n  r ec e ntl y  
d e m o nstr at e d t o c o nf er b e n efit o n critic all y ill C O VI D- 1 9 p a ti e nts w h o pr o gr ess t o pr of o u n d i nfl a m m ati o n of t h e l u n g 
ass oci at e d c yt o ki n e st or m a n d A R D S( 3 8, 3 9). W e h y p ot h esiz e t h at U C- M S C t h er a p y (i n v esti g ati o n al pr o d uct) r e pr es e nts 
a vi a bl e t h er a p e utic o pti o n f o r s u bj ects wit h s e v er e c as es of C O VI D- 1 9, u n d er g oi n g c yt o ki n e st or m l e a di n g t o A R D S. 
S p ecific ai ms of t h e pr o p os e d R C T i n s u bj ects wit h s e v er e C O VI D 1 9 will i ncl u d e:  
 
S p ecific Ai m 1 :  D et er mi n ati o n of t h e s af et y of I V i nf usi o ns of t h e all o g e n eic U C- M S C t h er a p y (i n v esti g ati o n al 
pr o d uct).   All s u bj ects will b e f oll o w e d f or 9 0 d a ys f oll o wi n g tr e at m e nt. S af et y e n d p o i nts will b e ass ess e d b y m o nit ori n g 

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a d v ers e e v e nts ( A Es) f or 6 h o urs f oll o wi n g tr e at m e nt, a n d s e ri o us a d v ers e e v e nts ( S A Es) fr o m e nr oll m e nt t hr o u g h d a y 9 0 
p ost i nt er v e nti o n.  
S p ecific Ai m 2 : E x pl or e effic ac y of t h e all o g e n eic U C- M S C t h er a p y (i n v esti g ati o n al pr o d uct) a d mi nist er e d I V i n a d ult 
I C U- C O VI D- 1 9 p ati e nts, di a g n os e d wit h A R D S, i n a m ulti-c e nt er, c o ntr oll e d, r an d o miz e d cli nic al tri al.  Ex pl or at or y 
effic ac y o utc o m es will b e ass ess e d usi n g cli nic al o utc o m es t h at i ncl u d e s ur vi v al, v e ntil at or-fr e e d a ys, ox y g e n ati o n i n d ex 
( OI), dri vi n g pr ess ur e ( Pl at – P E E P), s e q u e nti al or g a n f ail ur e ass ess m e nt ( S O F A), a n d c h a n g es i n l a b or at or y i n dic at ors 
( C B C, c o m pl et e m et a b olic p a n el, i nfl a m m at or y p a n el, D- di m er, Vit a mi n D l e v els, P R A).  T o c o nfir m effic ac y, w e will als o 
p erf or m c o m pr e h e nsi v e a n al ysis of c h a n g es i n  (i) l y m p h oc yt e s u bs ets, (ii) c yt o ki n e profil es, (iii) acti vit y m ar k ers. T his ai m 
is b as e d o n r es ults r e p ort e d b y s e v er al st u di es of M S C i nf usi o n l e a di n g t o c h a ng es i n t h e i m m u n e mili e u i ncl u di n g T-r e g 
c ell n u m b er a n d f u ncti o n, c yt o ki n e pr ofil es, a n d tiss u e r e p air.   
 
T h e d e v el o p m e nt of n o v el tr e at m e nt o pti o n f or C O VI D- 1 9 p ati e n ts is of p ar a m o u nt i m p ort a nc e. R es ults fr o m t his tri al  
will b e of assist a nc e t o d esi g n l ar g er P h as e 2 b m ulti-c e nt er R C Ts n ec ess ar y t o d e al wit h t h e i ncr e asi n g p ati e nts p ositi v e 
f or S A R S- C o V- 2 vir us. 
B ack gr o u n d 
A hi g hl y c o nt a gi o us c or o n a vir us, S A R S - C o V- 2 ( pr e vi o usl y k n o w n as 2 0 1 9- n C o V), h as s pr e a d r a pi dl y ar o u n d t h e w orl d, 
c a usi n g a s h ar p ris e of a p n e u m o ni a-li k e dis e as e t er m e d C or o n a vir us Dis e as e 2 0 1 9 ( C O VI D- 1 9) ( 1, 2). C O VI D- 1 9 pr es e nts 
a hi g h m ort alit y r at e, esti m at e d at 3. 4 %, a n d t h e W orl d H e alt h Or g a niz ati o n h as cl assifi e d it as a p a n d e mic ( 3). T h e r a pi d 
s pr e a d of t h e vir us ( esti m at e d r e pr o d ucti v e n u m b er R 0 2. 2 – 3. 6 ( 4, 5)) is c a usi n g a si g nific a nt s ur g e of p ati e nts r e q uiri n g 
i nt e nsi v e c ar e. M or e t h a n 1 o ut of 4 h os pit aliz e d C O VI D- 1 9 p ati e nts h a v e r e q uir e d a d missi o n t o a n I nt e nsi v e C ar e U nit 
(I C U) f or r es pir at or y s u p p ort, a n d a l ar g e pr o p orti o n of t hes e I C U- C O VI D- 1 9 p ati e nts, b et w e e n 1 7 % a n d 4 6 %, h a v e di e d 
( 6- 1 0). A c o m m o n o bs er v ati o n a mo n g p ati e nts wit h s e v er e C O VI D- 1 9 i nf ecti o n is a n i nfl a m m at or y r es p o ns e l oc aliz e d t o 
t h e l o w er r es pir at or y tr act ( 1 1- 1 3). T his i nfl a m m ati o n, ass oci at e d wit h d ys p n e a a n d h y p ox e mi a, i n s o m e c as es e v ol v es 
i nt o  exc essi v e  i m m u n e  r es p o ns e  wit h  c yt o ki n e  st or m,  d et er mi ni n g  pr o gr essi o n  t o  Ac ut e  L u n g  I nj ur y  ( ALI),  Ac ut e  
R es pir at or y Distr ess S y n dr o m e ( A R D S), or g a n f ail ur e, a n d d e at h ( 2, 1 0). C or o n a vir us m ort alit y is cl e arl y ass oci at e d wit h 
A R D S a n d m ulti pl e or g a n f ail ur e ( 7, 4 4).  B ot h of t h es e p at h ol o gi es h a v e b e e n d e m o nstr at e d t o b e c a us e d b y c yt o ki n e 
st or m, w hic h c a us es fl ui d l e a k a g e a n d diss e mi n at e d i ntr a v asc ul ar c o a g ul ati o n ( 4 5, 4 6).  A R D S is a r a pi dl y pr o gr essi v e 
dis e as e c h ar act eriz e d b y diff us e i nfl a m m ati o n a n d i ncr e as e d v asc ul ar p er m e a bilit y of t h e l u n g p ar e nc h y m a, l e a di n g t o 
i m p air e d al v e ol ar g as exc h a n g e ( 4 7, 4 8). A R D S m ort alit y h as b e e n esti m at e d t o b e i n t h e r a n g e of 3 5 % t o 4 6 % ( 4 9). 
Alt h o u g h  h e alt h  c ar e  a d v a nc e m e nts  h a v e  i m pr o v e d  p ati e nt  o utc o m es,  n o  p h ar m ac ol o gic al  tr e at m e nt  h as  s h o w n  
t h er a p e utic eff ecti v e n ess t o d at e. 
 
Dr ac o ni a n m e as ur es h a v e b e e n p ut i n pl ac e i n a n att e m pt t o c urt ail t h e i m p act of t h e C O VI D- 1 9 e pi d e mic o n p o p ul ati o n 
h e alt h a n d h e alt hc ar e s yst e ms. At t h e pr es e nt ti m e, t h er e is n eit h er a v acci n e n or s p ecific a nti vir al tr e at m e nts f or 
s eri o usl y  ill  p ati e nts  i nf ect e d  wit h  C O VI D- 1 9.  Cr uci all y,  n o o pti o ns  ar e  a v ail a bl e  f or  t h os e  p ati e nts  wit h  r a pi dl y  
pr o gr essi n g A R D S e v ol vi n g t o or g a n f ail ur e. Alt h o u g h s u p p orti v e c ar e (i ncl u di n g m ec h a nic al v e ntil ati o n a n d s u p p ort of 
vit al or g a n f u ncti o ns) is pr o vi d e d w h e n e v er p ossi bl e, it is i ns uffici e nt i n m ost s e v er e c as es. T h er ef or e, t h er e is a n ur g e nt 
n e e d  f or  n o v el  t h er a pi es  t h at  c a n  d a m p e n  t h e  exc essi v e  i nfl a m m at or y  r es p o ns e  i n  t h e  l u n gs  ass oci at e d  wit h  t h e  
i m m u n o p at h ol o gic al c yt o ki n e st or m, a n d t h at c a n acc el er at e t h e r e g e n er ati o n of f u ncti o n al l u n g tiss u e i n C O VI D- 1 9 
p ati e nts.   
 
M es e nc h y m al St e m C ells ( M S Cs) ar e p ot e nt i m m u n o m o d ul at or y c e lls t h at r ec o g niz e sit es of i nj ur y, li mit eff ect or T c ell 
r e acti o ns, a n d sti m ul at e r e g ul at or y c ell p o p ul ati o ns (i. e., T-r e gs) vi a gr o wt h f act ors, c yt o ki n es, a n d ot h er m e di at ors. 
Si m ult a n e o usl y, M S Cs als o sti m ul at e l oc al tiss u e r e g e n er ati o n vi a p ar acri n e eff ects i n d uci n g a n gi o g e nic, a nti-fi br otic a n d 
r e m o d eli n g r es p o ns es ( 1 4). C o ns e q u e ntl y, M S Cs- b as e d t h er a p y r e pr es e nts a vi a bl e tr e at m e nt o pti o n f or a ut oi m m u n e 
c o n diti o ns  a n d  ot h er  i nfl a m m at or y  dis or d ers  ( 1 5- 2 0),  yi el di n g  b e n efici al  eff ects  i n  m o d els  of  a ut oi m m u n e  T y p e  1  
Di a b et es  ( 2 1- 2 7),  S yst e mic  L u p us  Er yt h e m at os us,  A ut oi m m u n e  E nc e p h al o m y elitis  ( 2 8),  M ulti pl e  Scl er osis  ( 2 9,  3 0),  

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c ar di ac i ns uffici e nc y ( 3 1, 3 2), a n d or g a n tr a ns pl a nt ati o n ( 3 3). M S Cs h a v e b e e n r e p ort e d t o i n hi bit i nfl a m m ati o n a n d 
fi br osis i n t h e l u n gs ( 3 4- 3 7), h a v e s h o w n s af et y i n cli nic al tri als f or A R D S( 5 0- 5 3). B e n efici al eff ects fr o m c ell t h er a p y w er e 
o bs er v e d i n a ni m al m o d els, a n d extr ac or p or e al l u n g m o d els of A R D S ( 5 4, 5 5).  M S C fr o m a di p os e ( 5 6- 5 9), b o n e m arr o w 
( 6 0- 7 9), pl ac e nt al ( 8 0), a mni otic m e m br a n e ( 8 1, 8 2), u m bilic al c or d ( 8 3- 8 9), m e nstr u al bl o o d ( 9 0), a n d l u n g ( 9 1, 9 2) 
ori gi n, as w ell as c o n diti o n e d m e di a ( 9 3- 1 0 0), h a v e d e m o nstr at e d r e d ucti o n of p ul m o n ar y i nj ur y, w at er l e a k a g e, a n d 
n e utr o p hil acc u m ul ati o n.  A n a n al ysis of 3 4 2 s yst e mic i nf usi o ns a n d 5 7 br o nc hi al i n still ati o ns ( 2 0 4 r eci pi e nts) of c ells of 
v ari o us ori gi ns f or A R D S a n d ot h er p ul m o n ar y iss u es d e m o nstr at e d s af et y i n e arl y cli nic al tri als ( 5 2, 1 0 1).   S e v er al r ec e nt 
cli nic al tri als h a v e a d dr ess e d t h e s af et y  a n d effic ac y of t h e e arl y M S C p o p ul ati o n d eri v e d fr o m pl ac e nt al tiss u e ( 1 0 2- 1 0 5).  
 
M S C h a v e b e e n r ec e ntl y s u g g est e d as us ef ul t o tr e at p ati e nts  wit h s e v er e C O VI D- 1 9 b as e d o n t h eir eff ects pr e v e nti n g or 
att e n u ati n g t h e i m m u n o p at h o g e nic c yt o ki n e st or m ( 3 8- 4 1). M S Cs c a n b e e asil y d eri v e d i n l ar g e n u m b ers fr o m t h e 
U m bilic al C or d ( U C) a n d c a n b e r a pi dl y ex p a n d e d i nt o cl i nic all y-r el e v a nt n u m b ers ( 4 2). U C- M S C h a v e d e m o nstr at e d 
s af et y a n d effic ac y i n cli nic al tri als, a n d h a v e b e e n s af el y a d mi nist er e d acr oss hist oc o mp ati bilit y b arri ers ( 1 0 2- 1 0 5). U C-
M S Cs  pr oc ess e d  at  o ur  f acilit y  h a v e  b e e n  r ec e ntl y  i ntr o d uc e d  i ntr a v e n o usl y  i n  p ati e nts  wit h  a  n e ur o d e g e n er ati v e  
dis or d er( 4 3), a n d h a v e b e e n a p pr o v e d f or t esti n g i n p ati e nts wit h T y p e 1 Di a b et es.  
 
Li a n g et al d e m o nstr at e d t h at a n i nf usi o n of U C- M S C w as w ell t ol er at e d a n d r es u lt e d i n si g nific a nt cli nic al i m pr o v e m e nt 
i n a critic al 6 5- y e ar- ol d p ati e nt w h o t est e d p ositi v e f or C O VI D- 1 9 ( 3 9). L e n g et al tr e at e d s e v e n C O VI D- 1 9 p ositi v e 
p n e u m o ni a p ati e nts wit h eit h er B o n e M arr o w- d eri v e d M S Cs ( B M- M S Cs) or U C- M S Cs. T h e gr o u p r e p ort e d t h at at 2 d a ys 
f oll o wi n g tr a ns pl a nt ati o n, p ul m o n ar y f u ncti o n a n d cli nic al s y m pt o ms (i m pr o v e d ox y g e n s at ur ati o n a n d r e d uc e d f e v er) i n 
t h es e p ati e nts w er e i m pr o v e d, wit h o ut a n y o bs er v a bl e a d v ers e e v e nts ( 3 8). A m o n g s e v e n p ati e nts tr e at e d wit h B M- a n d 
U C- M S Cs, f o ur r ec o v er e d a n d w er e disc h ar g e d fr o m t h e h os pit al 1 0 d a ys f oll o wi n g tr e at m e nt. T w o of t h es e p ati e nts 
w er e critic al.  Ass ess m e nt  of p ati e nt s a m pl es i n dic at e d  t h at  M S C tr e at m e nt l e a d t o i m pr o v e m e nt  i n l y m p h o p e ni a,  
d ecr e as e d l e v els of C-r e acti v e pr ot ei n, r e d ucti o n a n d e v e n t u al dis a p p e ar a nc e of c yt o ki n e s ecr eti n g C X C R 3 + C D 4, C D 8 
a n d N K c ells ( wit hi n 3 d a ys of tr e at m e nt), dr a m atic i ncr e as e i n r e g ul at or y D C c ell p o p ul ati o n ( C D 1 4 + C D 1 1c + C D 1 1 b mil d ), 
i ncr e as e d  IL- 1 0  l e v els,  a n d  si g nific a ntl y  r e d uc e d  T N F-α  l e v els  ( 3 8).  A d diti o n all y,  M S Cs  w er e  d e m o nstr at e d  t o  b e  
u nif or ml y A C E 2 n e g ati v e, w hic h s h o ul d pr ecl u d e  i nf ecti o n of t h es e c ells fr o m S A R S- C o V- 2. 
 
T h es e st u di es d e m o nstr at e t h at M S Cs r e pr es e nt s af e a n d i n n o v ati v e a p pr o ac h t o tr e at m e nt of C O VI D- 1 9 p ati e nts w h o 
pr o gr ess t o critic all y s e v er e c as es of AL I, A R D S a n d/ or or g a n f ail ur e. M S C s o urc e tiss u e m a y als o pl a y a r ol e. C o m p ar e d t o 
B M-  or  a di p os e  tiss u e- d eri v e d  M S Cs  ( A D- M S Cs),  U C- M S C  c a n  b e  e asil y  is ol at e d  fr o m  wi d el y  a v ail a bl e  a n d  e asil y  
r etri e v a bl e U C, ex p a n d e d t o a cli nic all y r el e v a nt d os e o v er a r el ati v el y s h ort p eri o d of ti m e, ex pr ess pl uri p ot e nt m ar k ers 
O C T 4 a n d S O X 2, a n d ar e a bl e t o m ai nt a i n ex p a nsi o n c a p acit y f or > 9 0 p o p ul ati o n d o u bli n gs wit h o ut s e n esc e nc e, c h a n g es 
i n m or p h ol o g y or l oss of m ulti-li n e a g e diff er e nti ati o n p ot enti al ( 4 2, 1 0 6). T h e s af et y of U C- M S C c ell p o p ul ati o n w as 
d e m o nstr at e d i n s e v er al cli nic al tri als c o n d uct e d i n p ati e nts wit h T 1 D, c ar di ac i ns uffici e nc y ( 2 6, 3 1, 3 2) a n d n o w C O VI D-
1 9 ( 3 8, 3 9). Gi v e n t h e a bs e nc e of  a n a p pr o v e d v acci n e, gi v e n t h e s e v er e li mit atio ns of t h er a p e utic o pti o ns f or critic all y ill 
C O VI D- 1 9 p ati e nts, a n d gi v e n t h e r ec e nt cli nic al e vi d e nc e of s a f et y a n d effic ac y( 3 1, 3 2, 3 8, 3 9), w e b eli e v e t h at U C- M S Cs 
h a v e s u bst a nti al p ot e nti al f or t h e tr e at m e nt of C O VI D- 1 9 p a ti e nts wit h s e v er e dis e as e, u n d er g oi n g c yt o ki n e st or m 
l e a di n g t o A R D S. 
 

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R es e arc h str at e gy 
Si g nific a nc e 
T h e c or o n a vir us dis e as e 2 0 1 9 ( C O VI D- 1 9) is  a n ac ut e r es pir at or y dis e as e, c a us e d b y a n o v el f or m of c or o n a vir us ( S A R S-
C o V- 2), pr e vi o usl y k n o w n as 2 0 1 9- n C o V. T h e dis e as e w as first r e p ort e d w h e n a cl ust er of p ati e nts wit h p n e u m o ni a of 
u n k n o w n ori gi n w as i d e ntifi e d. All p ati e nts  i n t h e ori gi n al cl ust er w er e e pi d e mi ol o gic all y i n k e d t o a s e af o o d m ar k et i n 
W u h a n, H u b ei pr o vi nc e, C hi n a ( 1, 2). C O VI D- 1 9 h as s pr e a d t hr o u g h o ut t h e g e n er al p o p ul ati o n r a pi dl y a n d o n J a n u ar y 
3 0 t h, 2 0 2 0, W H O offici all y d ecl ar e d C O VI D- 1 9 a p u blic h e alt h e m er g e nc y of i nt er n ati o n al c o nc er n ( W H O). O n M arc h 
1 1, W H O c h ar act eriz e d C O VI D- 1 9 as a p a n d e mic ( 3). S A R S- C o V- 2 is a pr e vi o usl y u n k n o w n b et ac or o n a vir us, a n e n v el o p e d 
R N A vir us tr a ns mitt e d a m o n g h u m a n b ei n gs, ot h er m a m m als, a n d bir ds. T h e vir us h as a z o o n otic m o d e of tr a ns missi o n, 
a n d o nc e i ntr o d uc e d i nt o h u m a ns, is s pr e a d m ai nl y t hr o u g h p e rs o n-t o- p ers o n c o nt act. It c a us es r es pir at or y, e nt eric, 
h e p atic a n d n e ur ol o gic dis e as es ( 1, 2). S A R S- C o V- 2 is a m e m b er of t h e c or o n a vir us f a mil y wit h six pr e vi o usl y k n o w n 
f or ms. Ot h er w ell- k n o w n m e m b ers of t h e c or o n a vir us f a mil y ar e S A R S- C o V- 1 a n d M E R S- C o V, w hic h c a us e r es pir at or y 
dis e as es wit h a hi g h er c as e f at alit y r at e c o m p ar e d t o S A R S- C o V- 2. S e q u e nci n g st u di es p oi nt t o t h e f act t h at S A R S- C o V- 2 
h as a n al m ost i d e ntic al g e n o m e t o b at c or o n a vir us, p oi nti n g  t o b at as t h e n at ur al h ost. R ec e nt st u di es p erf or m e d i n 
C hi n a ( 1, 2, 1 2, 3 8- 4 0) d e m o nstr at e t h at S A R S- C o V- 2 us es t h e s a m e r ec e pt or, a n gi ot e nsi n-c o n v erti n g e nz y m e 2 ( A C E 2), 
pr e v al e nt i n h u m a n e pit h eli a of t h e l u n g a n d s m all i nt esti n e, as w ell as v asc ul ar e n d ot h eli u m ( 1 0 7, 1 0 8). H e nc e, t h e m ai n 
t ar g et of t h e vir us is t h e r es pir at or y tr act, a n d i nf ecti o n l e a ds t o fl u-li k e cli nic al s y m pt o ms. El d erl y i n di vi d u als, es p eci ally 
t h os e wit h c o- m or bi diti es, ar e at hi g h er ris k f or s eri o us, critic al a n d e v e n f at al cli nic al o utc o m es ass oci at e d wit h ALI, 
A R D S, or g a n f ail ur e a n d d e at h ( 1, 3). St u di es s h o w t h at C O VI D- 1 9 dis e as e m a nif est e d i n critic al cli nic al s y m pt o ms is 
cl os el y ass oci at e d wit h c yt o ki n e st or m ( 2, 3 8- 4 0).  
 
Pr e vi o us tiss u e distri b uti o n st u di es d e m o nstr at e d t h at t h e A C E 2 r ec e pt or is n ot ex pr ess e d o n i m m u n e c ell p o p ul ati o ns - 
w hic h i ncl u d e T a n d B c ells, m acr o p h a g e s a n d M S Cs ( 1 0 7). T his s u g g est t h at i m m u n e t h er a pi es c o ul d b e utiliz e d f or t h e 
tr e at m e nt of C O VI D- 1 9 dis e as e. 
 
 M S Cs ar e a d ult st e m c ells wit h a bilit y t o diff er e nti at e i nt o a di p oc yt e, c h o n dr oc yt e a n d ost e oc yt e, a n d c a n b e is ol at e d 
fr o m a v ari et y of tiss u es i ncl u di n g B M, a di p os e, pl ac e nt al, U C, a n d v asc ul ar tiss u e, etc. ( 1 0 9). T h es e c ells pr es e nt a 
fi br o bl ast-li k e m or p h ol o g y, ex pr ess c ell s urf ac e m ar k ers C D1 0 5, C D 7 3 a n d C D 9 0, a n d l ac k ex pr essi o n of C D 4 5, C D 3 4, 
C D 1 1 b, C D 1 9 a n d HL A- D R ( 1 0 9). M S Cs ex pr ess m o d er at e l e v e ls of m aj or hist oc o m p ati bilit y c o m pl ex ( M H C) cl ass I 
m ol ec ul es a n d v er y littl e or n o M H C cl ass II ( 1 1 0), w hic h all o ws f or tr a ns pl a nt ati o n acr oss M H C b arri ers. M S Cs h a v e b e e n 
r e p ort e d t o h a v e b ot h i m m u n o m o d ul at or y a n d r e g e n er ati v e pr o p erti es a n d mi g ht r e pr es e nt a pr o misi n g i nt er v e nti o n 
wit h e vi d e nc e of t ar g eti n g s e v er al i nj ur y p at h w a ys i n a n u m b er of i nfl a m m at or y a n d a ut oi m m u n e c o n diti o ns. M S Cs’ 
i m m u n os u p pr essi v e  c a p acit y  is  b as e d  o n  t h eir  a bilit y  t o  pro d uc e  nitric  oxi d e,  i n d ol e a m i n e  2, 3  di ox y g e n as e  (I D O),  
tr a nsf or mi n g gr o wt h f act or β  ( T G Fβ ), pr ost a gl a n di n E 2 ( P G E 2), m atrix m et all opr ot ei n as es ( M M Ps), i n t erl e u ki n 1 0 (IL- 1 0), 
a n d ot h er m e di at ors ( 1 5- 1 9). M S Cs’ i m m u n o m o d ul at or y f u ncti o n w as d e m o nstr at e d  i n A E ( 2 8), SL E ( 1 1 1, 1 1 2), T 1 D ( 2 5-
2 7), m ulti pl e scl er osis ( M S) ( 2 9,  3 0), Gr aft- vs- H ost Dis e as e ( G v H D) ( 2 1), art hritis, a n d r ec e ntl y i n p ati e nts wit h C O VI D- 1 9 
( 3 8- 4 0). D u e t o t h e ur g e nc y of t h e sit u ati o n, cr e at e d b y a n acc el er at e d S A R S- C o V- 2 tr a ns missi o n, s m all a ni m al a n d pr e-
cli nic al m o d els d at a o n t h e m o d e of ac ti o n of S A R S- C o V- 2 vir us is u n a v ail a bl e. Als o u n a v ail a bl e at t h e pr es e nt ti m e ar e a 
C O VI D- 1 9 v acci n e or p h ar m ac ol o gic al a g e nts a p pr o v e d t o tr e at p ati e nts wit h t h e m ost s e v er e f or ms of t h e dis e as e, i. e. 
t h os e di a g n os e d wit h ALI a n d A R D S. I n t h e a bs e nc e of a n y tre at m e nt m o d aliti es, wit h t h e exc e pti o n of s u p p orti v e c ar e 
gi v e n t o t h e critic all y ill, w e pr o p os e t h at M S C- b as e d c ell ul ar  t h er a pi es mi g ht r e pr es e nt a vi a bl e o pti o n t o tr e at p ati e nts 
wit h critic al ill n ess r el at e d t o C O VI D- 1 9, w h o d e v el o p ALI, A R D S a n d, i n s o m e  c as es, or g a n f ail ur e.  
 

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M S Cs h a v e d e m o nstr at e d g o o d s af et y pr ofil e wit h n o ris k of t u m or f or m ati o n ( 2 6, 1 1 3, 1 1 4) . A ut ol o g o us an d all o g e n eic 
B M-, U C- a n d A D- d eri v e d M S Cs h a v e b e e n utiliz e d f or w o u n d h e ali n g a n d ar e b ei n g t est e d i n a ni m al m o d els a n d cli nic al 
tri als f or t h e tr e at m e nt of a ut oi m m u n e a n d i nfl a m m at or y dis e as e ( 1 1 1, 1 1 2, 1 1 5) , T 1 D ( 2 1- 2 7), A R D S ( 3 8- 4 1), a n d n o w 
C O VI D- 1 9 ( 3 8- 4 0). T h es e e arl y st u di es utiliz e d B M- a n d U C- d eri v e d M S C, d e m o nstr ati n g s af et y a n d pr eli mi n ar y effic ac y 
m a nif est e d b y i m pr o v e d p ul m o n ar y f u ncti o n, r es ol uti o n of a c yt o ki n e st or m a n d i ncr e as e i n r e g ul at or y i m m u n e c ell 
p o p ul ati o n C O VI D- 1 9 ( 3 8- 4 0). T his r es e m bl e s t h e sit u ati o n d e m o nstr at e d i n a ni mal m o d els of T 1 D ( 1 1 6- 1 2 0) , w h er e 
M S C w er e d e m o nstr at e d t o mi gr at e t o t h e cit e of i nj ur y, i. e. p a ncr e as, a n d pr e v e nt e d t h e d estr ucti o n of t h e p a ncr e atic 
isl ets ( 1 1 6). A n ot a bl e r e d ucti o n i n a ut or e acti v e T-c ell p o p ul ati o n, i ncr e as e i n t h e T-r e g p o p ul ati o n al o n g wit h t h e 
r e d ucti o n i n pr o-i nfl a m m at or y c yt o ki n es i n t h e ex p eri m e nt al a ni m als w as als o o bs er v e d a n d l e d t o t h e c o ncl usi o n t h at 
U C- M S C ( WJ- M S Cs) i n hi bit t h e ex p a nsi o n of a ut or e acti v e T-c e ll p o p ul ati o n b y i n d uci n g T-r e gs a n d m o dif yi n g t h e c yt o ki n e 
pr ofil e ( 1 1 6, 1 1 8). Fr e q u e nci es of C D 4 + C D 2 5 + F ox p 3 + T-r e gs i n t h e tr e at m e nt gr o u p w er e hi g h er, w hil e l e v els of pr o-
i nfl a m m at or y c yt o ki n es, IL- 2, I F N- g, T N F-α , a n d d e gr e e of i ns ulitis w er e l o w er i n tr e at m e nt vs c o ntr ol gr o u p ( 1 1 8). 
Si mil ar r es ults w er e r e p ort e d f or SL E a n d A E ( 1 1 1, 1 1 2, 1 1 5, 1 2 1).  
 
M S C s o urc e m a y als o pl a y a r ol e ( 4 2). U C- M S C c a n b e d eri v e d m uc h f ast er a n d e asi er d u e t o a wi d e a v ail a bilit y of t h e 
s o urc e tiss u e, i. e. U C. L ar g e n u m b er of M S Cs c a n b e g e n er at e d fr o m a si n gl e U C a n d r a pi dl y ex p a n d e d i nt o cli nic all y-
r el e v a nt n u m b ers. A p o p ul ati o n of U C- M S Cs of i nt er est t o t his pr oj ect w as d e m o nstr at e d t o m ai nt ai n its ex p a nsi o n 
c a p acit y o v er 9 0 p o p ul ati o n d o u bli n gs wit h o ut c ell s e n esc e nc e, w hil e m ai nt ai ni n g M S C c h ar act eristics a n d f u ncti o ns 
( 4 2). 
 
I n n ov ati o n 
T ar g et e d s u p pr essi o n of t h e i m m u n e s yst e m  usi n g c ell ul ar t h er a pi es h as t h e p ot e nti al t o s hift t h e tr e at m e nt p ar a di g m i n 
p ati e nts wit h critic al f or ms of C O VI D- 1 9. L ac k of a n a p pr o v e d v acci n e a n d ot h er tr e at m e nts wit h t h e exc e pti o n of 
s u p p orti v e t h er a p y f or pr o p er or g a n f u ncti o n, al o n g wit h t h e n ec essit y t o c urt ail t h e w orl d- wi d e e pi d e mic ass oci at e d 
wit h C O VI D- 1 9 n ec essit at es t h e d e v el o p m e nt of alt er n ati v e t h er a pi es. C ell ul ar t h er a pi es h a v e g ai n e d m o m e nt u m i n t h e 
l ast 2 0 y e ars a n d h a v e b e e n s ucc essf ull y us e d i n t h e cli nic. T h e s af et y a n d effic ac y of M S Cs h a v e b e e n cl e arl y 
d e m o nstr at e d i n a n u m b er of cli nic al tr i als. F or t his pr oj ect w e ar e pr o p osi n g t o us e a n o v el p o p ul ati o n of M S C, d eri v e d 
fr o m a si n gl e U C. T h e sc arcit y of U C- M S C t h er a pi es m a n uf act ur e d a n d t est e d acc or di n g t o a p plic a bl e F D A r e g ul ati o ns, 
pr ecl u d es t h e us e of t h es e pr o d ucts i n cli nic al tri als ai m e d t o ex pl or e t h eir s af et y a n d eff ecti v e n ess. C o m p ar e d t o ot h er 
tiss u e s o urc es, U C- M S C c a n b e e asil y d eri d e d fr o m a wi d el y a v ail a bl e U C tiss u e a n d a cli nic al d os e ac hi e v e d at a l o w er 
c ult ur e p ass a g e. U C- M S Cs w er e s h o w n t o ex pr ess O C T 4 a n d S O X 2 pl uri p ot e nc y m ar k ers a n d c a n b e c ult ur e d f or > 9 0 
p o p ul ati o n d o u bli n gs wit h o ut s e n esc e nc e, m or p h ol o gic al c h a n g e s or l oss of m ulti-li n e a g e diff er e nti ati o n p ot e nti al ( 4 2, 
1 0 6). W e ai m t o utiliz e d a pr e vi o usl y d e v el o p e d u n d er c G M P c o n diti o ns a n d t est e d U C- M S C M C B, cr e at e d fr o m a U C 
c oll ect e d fr o m a h e alt h y m ot h er wit h a n or m al pr e g n a nc y,  at t h e e n d of d eli v er y. A u ni q u e f e at ur e of o ur U C- M S C 
m a n uf act uri n g pr oc ess, n ot c o m m o n t o m ost M S C d eri v ati o n or c u lt ur e s yst e ms, is t h at it is fr e e of x e n o g e n eic pr ot ei ns 
a n d/ or a n y a ni m al- d eri v e d pr o d ucts ( 3 2, 4 2, 1 2 2). T h e U C- M S C M C B w e pl a n t o utiliz e i n t his cli nic al tri al h as b e e n 
t est e d t o ass ur e its s af et y, i d e ntit y, p urit y, p ot e nc y a n d effic ac y, acc or di n g t o a p plic a bl e F D A r e g ul ati o ns. Cli nic al gr a d e 
U C- M S C fi n al pr o d uct, m a n uf act ur e d fr o m t h e est a blis h e d U C - M C B, will b e utiliz e d t o tr e at critic al C O VI D- 1 9 p ati e nts 
t h at pr o gr ess t o ALI/ A R D S.( 3 8- 4 0) ( 2 6, 3 1, 3 2, 3 8- 4 0, 4 2, 5 1, 5 9).  
 
St u dy D esi g n a n d M et h o ds  
R es e arc h T e a m: 
O ur t e a m’s ext e nsi v e ex p eri e nc e wit h c ell- b as e d pr o d ucts d e v el o p m e nt, c h ar act eriz ati o n, a n d utiliz ati o n i n cli nic al tri als, 
will  b e  of  assist a nc e  t o  t h e  s ucc essf ul  ex ec uti o n  of  t h e  pr o p os e d  cli nic al  tri al,  i n  c o ll a b or ati o n  wit h  k e y  U S  a n d  
i nt er n ati o n al ex p erts i n i nf ecti o us dis e ase, p ul m o n ar y m e dici n e a n d critic al c ar e.   

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
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C o nfi de ntial
  
  
C a mill o Ric or di, M D , st u d y PI, is t h e St ac y J o y G o o d m a n Pr of ess or of S ur g er y, Disti n g uis h e d Pr of ess or of M e dici n e, 
Pr of ess or of Bi o m e dic al E n gi n e eri n g, a n d Micr o bi ol o g y a n d I m m u n ol o g y at t h e U ni v ersit y of Mi a mi ( U M), Fl ori d a, w h er e 
h e s er v es as Dir ect or of t h e Di a b et es R es e arc h I nstit ut e ( D RI; w w w. di a b et esr es e arc h. or g ) a n d t h e C ell Tr a ns pl a nt C e nt er. 
Ric or di h as b e e n s er vi n g as H e a d of t h e NI H f u n d e d c G M P (c urr e nt G o o d M a n uf act uri n g Pr actic es) A d v a nc e d C ell a n d 
Bi ol o gic Pr o d uct M a n uf act uri n g F acilit y ( 1 9 9 3- pr es e nt), f or r es e arc h a n d cli nic al a p plic ati o ns at U M, i n t h e U S a n d 
w orl d wi d e. Ric or di h as r ec ei v e d n u m er o us h o n ors a n d a w ar ds, i ncl u di n g t h e W orl d Priz e i n S ur g er y ( U ni v ersit y of 
G e n e v a) f or d e v el o pi n g a t ec h n ol o g y t h at si g nific a ntl y c o nt ri b ut e d t o t h e a d v a nc e m e nt of a s ur gic al fi el d, a n d t h e 
O utst a n di n g Sci e ntific Ac hi e v e m e nt A w ar d b y t h e A m eric a n Di a b et es Ass oci ati o n. Ric or di w as K ni g ht e d b y t h e Pr esi d e nt 
of t h e R e p u blic of It al y i n t h e hi g h est Or d er of t h e R e p u blic (t h e Or d er of M erit) wit h t h e K ni g ht h o o d d ec or ati o n of 
C a v ali er e Uffici al e a n d h e w as o n e of t h e f e w s ur g e o ns e v er i n d uct e d i nt o t h e Ass oci ati o n of A m eric a n P h ysici a ns ( A A P). 
Ric or di is a f ell o w of t h e N ati o n al Ac a d e m y of I n v e nt ors, U S A, a n d a m e m b er of t h e It ali a n S u pr e m e C o u ncil of H e alt h. 
H e is r ec o g niz e d as a w orl d l e a d er i n i m m u n ot h er a p y, c ell r e pl ac e m e nt t h er a p y a n d isl et c ell tr a ns pl a nt ati o n. H e h as a 
v ast ex p eri e nc e i n c ell ul ar t h er a pi es a n d h as l e d a n d p artici p at e d a n u m b er of cli nic al tri als usi n g U C- M S C i n p ati e nts 
wit h T y p e 1 Di a b et es, or g a n tr a ns pl a nt ati o n a n d Alz h ei m er’s,  c o n d uct e d o v er t h e l ast 3 0 y e ars. Ric or di’s sci e ntific 
p u blic ati o ns: 1, 1 4 2; Cit ati o ns 4 4, 0 1 4; H-i n d ex 9 7. As a n i n v e nt or , h e h as b e e n a w ar d e d 2 7 p at e nts. Ric or di will o v ers e e, 
st e er, a n d m a n a g e t h e o v er all dir ecti o n of t his st u d y. 
 
 M aril y n K a y Gl ass b er g, M D,  st u d y C o- PI, is Pr of ess or of M edici n e at t h e U ni v ersit y of Ariz o n a C oll e g e of M e dici n e is t h e 
C hi ef, Di visi o n of P ul m o n ar y M e dici n e, Cr itic al C ar e, a n d Sl e e p; Vic e- C h air of Di v ersit y a n d I ncl usi o n a n d S e ni or Dir ect or 
of R es e arc h Str at e g y a n d Gr o wt h. S h e is a l e a di n g n ati o n al a n d i nt er n ati o n al ex p ert i n r ar e l u n g dis e as es a n d i di o p at hic 
p ul m o n ar y fi br osis. Dr. Gl ass b er g is a p h ysici a n sci e ntist f oc us e d o n t h e r ol e of a g e a n d s ex i n irr e v ersi bl e fi br otic a n d 
c hr o nic l u n g dis e as es. H er r es e arc h als o i n v ol v es st u di es f oc us e d o n t h e m ec h a nis m of ste m/str o m al c ell- b as e d t h er a p y 
i n t h es e i nc ur a bl e l u n g dis e as es 
 
  
Gi ac o m o L a nz o ni, P h D , st u d y C o- PI, is R es e arc h Assist a nt Pr of ess or at t h e Di a b et es R es e arc h I nstit ut e, D e p art m e nt of 
Bi oc h e mistr y a n d M ol ec ul ar Bi ol o g y, U ni v ersit y of Mi a mi. Dr. L a nz o ni h as 1 5 y e ars of ex p eri e nc e o n pl ac e nt a- a n d 
u m bilic al c or d- d eri v e d M S Cs. H e  h as ext e nsi v e ex p eri e nc e i n t h e d e v el o p m e nt a n d c h ar act eriz ati o n of M S C a n d st e m c ell 
pr o d ucts f or c ell t h er a p y. His m ai n i nt er est is o n t h e cli nic al tr a nsl ati o n of t h e i m m u n o m o d ul at or y a n d r e g e n er ati v e 
pr o p erti es of M S Cs. Dr. L a nz o ni h as ex p eri e nc e i n cli nic al tri al d esi g n a n d c o or di n ati o n. H e will b e r es p o nsi bl e f or t h e 
est a blis h m e nt of t h e U C- M S C c ult ur es f or t h e g e n er ati o n of U C- M S C M C B. M or e o v er, h e will b e r es p o nsi bl e f or t h e 
c h ar act eriz ati o n of t h e U C- M S C i m m u n o m o d ul at or y p ot e nc y, b ot h i n vitr o a n d i n tr e at m e nt r eci pi e nts, a n d h e will 
o v ers e e m ec h a nistic a n al ys es i n t h e cli nic al tri al. 
  
Eli n a Li n ets k y, P h D , C o- PI, will g e n er at e t h e U C- M S C M C B. Dr. Lin ets k y h as ext e nsi v e ex p eri e nc e i n pr o d uct 
d e v el o p m e nt, cli nic al r es e arc h i n t h e R e g e n er ati v e M e dici n e  ar e n a a n d, s p ecific all y, c ell ul ar t h er a p y m a n uf act ur e a n d 
pr o d uct r e g ul at or y d e v el o p m e nt.  S h e h as b e e n w or ki n g wit h t h e M S C pr o d ucts f or t h e l ast 1 5 y e ars, a n d is c o nsi d er e d 
t o b e a n ex p ert i n t h e fi el d of c ell ul ar t h er a pi es. O v er t h e y e ars, t h e F acilit y u n d er Dr. Li n ets k y`s l e a d ers hi p h as 
s u p p ort e d a n u m b er of D RI-, U M- a n d extr a m ur all y i niti at e d cli nic al tri als vi a c ell ul ar pr o d uct m a n uf act ur e, 
c h ar act eriz ati o n, a n d r e g ul at or y pr o d uct d e v el o p m e nt. F acilit y p ers o n n el ar e ex p eri e nc e d i n t h e m a n uf act ur e, 
c h ar act eriz ati o n, st or a g e a n d distri b uti o n of c ell ul ar t h er a pi es, p artic ul arl y M S C pr o d ucts fr o m v ari o us s o urc es. 
  
Di e g o C orr e a, M D, M Sc, P h D  st u d y C o- PI, h as 1 5 + y e ars of ex p eri e nc e c o n d ucti n g pr e-cli nic al a n d cli nic al r es e arc h i n t h e 
R e g e n er ati v e M e dici n e fi el d. H e h as ex p eri e nc e wit h i n vitr o a n d i n viv o a ni m al m o d els t o t est effic ac y of c ell- b as e d 
t h er a p y pr o d ucts o bt ai n e d fr o m m ulti pl e diff er e nt s o urc es ( b o n e m arr o w, a di p os e tiss u e, i nfr a p at ell ar f at p a d, 
e n d o m etri u m, u m bilic al c or d) a n d m a n uf act ur e d u n d er diff er e nt c o n diti o ns i ncl u di n g r e g ul at or y-c o m pli a nt pr ot oc ols. 
H e h as d e v el o p e d p ot e nc y ass a ys t esti n g M S C’s s ecr et or y a n d i m m u n o m o d ul at or y acti viti es, b as e d o n t h e d escri pti o n of 
p h e n ot y pic a n d f u ncti o n al r e a d o uts. A d diti o n all y, h e h as dir e ct e d cli nic al t e a ms a br o a d f oc us e d o n est a blis hi n g s af et y 
a n d effic ac y of c ell- b as e d pr o d ucts ( p oi nt of c ar e a n d c ult ur e- ex p a n d e d o n es) i n a n u m b er of cli nic al c o n diti o ns i ncl u di n g 
p eri p h er al v asc ul ar dis e as e ( P V D), c hr o nic ki d n e y dis e as e ( C K D) a n d ost e o art hritis ( O A). Al o n g wit h Drs L a nz o ni a n d 

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C o nfi de ntial
  
Li n ets k y, Dr C orr e a will c o ntri b ut e t o t h e c ell c h ar act eriz ati o n of U C- M S C b ef or e t h eir cli nic al us e i n p ati e nts e nr oll e d i n 
t his st u d y.  
  
R o dri g o Vi a n n a, M D, P h D, st u d y C o-I, Dir ect or, Mi a mi Tr a ns pl a nt I nstit ut e, C hi e f, Li v er, I nt esti n al a n d M ulti visc er al 
Tr a ns pl a nt. Pr of ess or of Cli nic al S ur g er y, U ni v ersit y of Mi a mi Mill er Sc h o ol of M e dici n e, J ac ks o n H e alt h S yst e m. Dr. 
Vi a n n a l e a ds t h e Mi a mi Tr a ns pl a nt I nstit ut e ( M TI), a u ni q u e affili ati o n b et w e e n J ac ks o n H e alt h S yst e m a n d U H e alt h – 
U ni v ersit y of Mi a mi H e alt h S yst e m, as dir ect or of M TI a n d c hi e f of li v er, i nt esti n al a n d m ulti visc er al tr a ns pl a nt. H e b e g a n 
his c ar e er as a f ell o w at J ac ks o n M e m ori al H os pit al m or e t h a n 1 5 y e ars a g o a n d r et ur n e d t o M TI aft er m ost r ec e ntl y 
s er vi n g as dir ect or of i nt esti n al a n d m ulti visc er al tr a ns pl a nt ati o n at I n di a n a U ni v ersit y H e alt h Tr a ns pl a nt. Dr. Vi a n n a is a 
pi o n e er i n i nt esti n al a n d m ulti visc er al tr a ns pl a nt ati o n. Si nc e his arri v al, M TI’s p ati e nt s u r vi v al a n d v ol u m es f or t h es e 
t y p es of tr a ns pl a nts h as b ec o m e o n e of t h e hi g h est i n t h e n ati o n. Dr. Vi a n n a is als o a n acc o m plis h e d li v er tr a ns pl a nt 
s ur g e o n, m a ki n g M TI’s li v er pr o gr a m o n e of t h e b est i n Fl ori d a. H e p erf or ms tr a ns pl a nts wit h s h ort er o p er ati n g ti m es 
a n d mi ni m al bl o o d l oss, w hic h ar e i n dic a t ors of b ett er l o n g-t er m o utc o m es. 
  
R o g er A. Al v ar ez, M D , st u d y C o-I, is a n Assist a nt Pr of ess or of M e dicin e at t h e U ni v ersit y of Mi a mi Mill er Sc h o ol of 
M e dici n e, w h er e his f oc us is tr a nsl ati o n al r es e arc h i n v ol vi n g a d v a nc e d l u n g dis e as es. His cli nic al w or k is d e dic at e d t o 
l e a di n g m ulti disci pli n ar y t e a ms t o c ar e f or p e o pl e c ar di o p ul m o n ar y dis e as es i ncl u di n g hi g h-ris k p ul m o n ar y e m b olis m 
a n d i nt erstiti al l u n g dis e as e, a n d c ari n g f or critic all y ill p ati e nts i n t h e i nt e nsi v e c ar e u nit, wit h s p eci al i nt er ests i n ac u t e 
l u n g i nj ur y a n d s h oc k. Dr. Al v ar ez c o m pl et e d his m e dic al tr ai ni n g at E m or y U ni v ersit y, a n d w e nt o n t o tr ai n i n P ul m o n ar y 
& Critic al C ar e M e dici n e at t h e U ni v ersit y of Pitts b ur g h, w h er e h e g ai n e d ex p eri e nc e i n t h e m a n a g e m e nt of s e v er e A R D S 
u n d er t h e m e nt ors hi p of pr o gr a m dir ect ors Drs. J o h n Kr eit a n d Br y a n Mc V err y. H e c o m pl et e d tr ai ni n g i n tr a nsl ati o n al 
p ul m o n ar y v asc ul ar r es e arc h u n d er t h e m e nt ors hi p of M ar k Gl a d wi n, M D a n d A d a m Str a u b, P h D, st u d yi n g m o d ul at ors 
of N O si g n ali n g a n d e n d ot h eli al d ysf u ncti o n i n p ul m o n ar y h y p ert e nsi o n. Aft er j oi ni n g t h e f ac ult y at t h e U M M S M, Dr. 
Al v ar ez br o u g ht his N O r es e arc h t o t h e b e dsi d e u n d er t h e m e nt ors hi p of Dr. M aril y n Gl ass b er g. H e c o m pl et e d a st u d y 
d eli v eri n g i n h al e d N O t o p ati e nts wit h IL D a n d p ul m o n ar y h y p ert e nsi o n, d e m o nstr ati n g si g nific a nt i m pr o v e m e nts i n 
h e m o d y n a mics d uri n g a n ac ut e- d os e esc al ati o n st u d y, w h er e h e p ers o n all y p erf or m e d h e m o d y n a mic st u di es i n I C U 
p ati e nts.  H e is als o PI of s e v er al i n d ustr y-s p o ns or e d tri als of n o v el dr u gs f or t h e tr e at m e nt of p ul m o n ar y art eri al 
h y p ert e nsi o n. Dr. Al v ar ez will o v ers e e t h e s el ecti o n of p ati e nts  wit h C O VI D- 1 9 f or p artici p ati o n i n t h e st u d y, p ers o n all y 
ass ess t h e p ati e nts at t h e U M sit e, a n d m o nit or t h eir c ar d i o p ul m o n ar y st at us d uri n g a n d aft er tr e at m e nt wit h t h e U C-
M S C. 
 
P hilli p R uiz, M D, P h D : st u d y C o-I,  is a Pr of ess or of S ur g er y a n d P at hol o g y, t h e M e dic al Dir ect or of t h e Tr a ns pl a nt 
L a b or at ori es, a n d Dir ect or of I m m u n o p a t h ol o g y at t h e U ni v ersit y of Mi a mi Mill er Sc h o ol of M e dici n e. H e is a n 
i nt er n ati o n all y r ec o g niz e d ex p ert i n tr a ns pl a nt ati o n- p at h ol o g y, i m m u n ol o g y, a n d i m m u n o p at h ol o g y. H e r ec ei v e d his 
P h. D. i n i m m u n ol o g y fr o m t h e U ni v ersit y of Fl ori d a, his M. D. fr o m G e or g e W as hi n gt o n U ni v ersit y, W as hi n gt o n, D C a n d 
his r esi d e nc y ( p at h ol o g y)/f ell o ws hi p tr ai ni n g at D u k e U ni v ersit y , N ort h C ar oli n a. H e h as b e e n at t h e U ni v ersit y of Mi a mi 
si nc e 1 9 8 9.. His r es e arc h i nt er ests i ncl u d e i m m u n e t ol er a nc e, s u bcli nic al r ej ecti o n, a n d t h e i nt er acti o n of i n m at e 
i m m u nit y wit h all or e acti vit y. H e h as m or e t h a n 5 5 0 p e er-r e vi e w e d j o ur n al articl es, n u m er o us b o o k c h a pt ers a n d is a 
fr e q u e ntl y i n vit e d s p e a k er at w orl d wi d e m e eti n gs. H e is o n t h e e dit ori al b o ar d a n d/ or a r e vi e w er of n u m er o us j o ur n als 
a n d a m e m b er of m a n y pr of essi o n al or g a niz ati o ns. H e is t h e Pr of ess or of S ur g er y a n d P at h ol o g y a n d M e dic al Dir ect or of 
I m m u n ol o g y a n d Hist oc o m p ati bilit y L a b or at or y (I HL) i n t h e D e p art m e nt of S ur g er y at Mi a mi, FL. H e als o s er v es as t h e 
Dir ect or of Cli nic al L a b or at ori es a n d Hist oc o m p ati bilit y L a b, A uxili o M ut u o H os pit al, S a n J u a n, P u ert o Ric o a n d Dir ect or 
of Cli nic al L a b or at ori es a n d Hist oc o m p a ti bilit y L a b, U ni v ersit y of Vir gi ni a M e dic al C e nt er, C h arl ott es vill e, Vir gi ni a 
 
 
Ar n ol d I. C a pl a n, P h D, st u d y C o-I, is Dr. C a pl a n is Pr of ess or of Bi ol o g y an d t h e Dir ect or of t h e S k el et al R es e arc h C e nt er at 
C as e W est er n R es er v e U ni v ersit y. Dr. C a pl a n r ec ei v e d his B. S. i n C h e mistr y at t h e Illi n ois I nstit ut e of T ec h n ol o g y, 
C hic a g o, Illi n ois; a n d his P h. D. fr o m T h e J o h ns H o p ki ns U ni v ersit y Sc h o ol of M e dici n e, B alti m or e, M ar yl a n d. Dr. C a pl a n 
di d a P ost d oct or al F ell o ws hi p i n t h e D e p art m e nt of A n at o m y at T h e J o h ns H o p ki ns U ni v ersit y, f oll o w e d b y P ost d oct or al 
F ell o ws hi ps at Br a n d eis U ni v ersit y, W alt h a m, M ass ac h us etts wit h Dr. N. O. K a pl a n  a n d Dr. E. Z willi n g. H e c a m e t o C as e 
W est er n R es er v e U ni v ersit y as Assist a nt Pr of ess or of Bi ol o g y i n 1 9 6 9 a n d r os e t hr o u g h t h e r a n ks t o b ec o m e Pr of ess or i n 

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S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
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C o nfi de ntial
  
1 9 8 1. H e h as t a k e n t hr e e s a b b atic al l e a v es: o n e i n 1 9 7 3 as a Visiti n g Pr of ess or i n t h e D e p art m e nt of Bi oc h e mistr y a n d 
Bi o p h ysics at t h e U ni v ersit y of C alif or ni a at S a n Fr a ncisc o M e dic al Sc h o ol wit h Bri a n Mc C art h y a n d Willi a m R utt er; o n e i n 
1 9 7 6 i n t h e I nstit ut e d e C hi mi e Bi ol o gi q u e  at t h e F ac ult y of M e dici n e d e Str as b o ur g i n t h e L a b or at or y of Pi err e 
C h a m b o n; a n d l astl y, t h e E d n a a n d J ac o b Mic h a el Visiti n g Pr of ess or of t h e D e p art m e nt of Bi o p h ysics wit h N at h a n S h ar o n 
at t h e W eiz m a n n I nstit ut e of Sci e nc e i n R e h o v ot, Isr a el i n 1 9 8 4. H e h as r ec ei v e d a n u m b er of a w ar ds i ncl u di n g t h e 
Eliz a b et h Wi nst o n L a ni er A w ar d gi v e n b y  t h e A m eric a n Ac a d e m y of Ort h o p a e dic S ur g e o ns as p art of t h eir 1 9 9 0 K a p p a 
D elt a A w ar ds Pr o gr a m, t h e 1 9 9 9 M ars h all R. Urist A w ar d f or Ex c ell e nc e i n Tiss u e R e g e n er ati o n R es e arc h gi v e n b y t h e 
Ort h o p a e dic R es e arc h S oci et y, t h e G e nz y m e Lif eti m e Ac hi e v e m e nt A w ar d gi v e n b y t h e I nt er n ati o n al C artil a g e R e p air 
S oci et y i n 2 0 0 7, t h e Tiss u e E n gi n e eri n g a n d R e g e n er ati v e M e dici n e I nt er n ati o n al S oci et y I n a u g ur al Lif eti m e Ac hi e v e m e nt 
A w ar d i n 2 0 1 0, is a n I n a u g ur al M e m b er of t h e “ Pi o n e ers of I n n o v ati o n” c h os e n b y t h e A d v oc ac y C o m mitt e e of t h e 
Ort h o p a e dic R es e arc h S oci et y, M arc h 2 0 1 4,  Lif eti m e Ac hi e v e m e nt A w ar d, N ati o n al C e nt er f or R e g e n er ati v e M e dici n e, 
A u g ust 2 0 1 5 a n d Lif eti m e Ac hi e v e m e nt A w ar d pr es e nt e d at I n t er n ati o n al J oi nt Pr es er v ati on C o n gr ess, S e pt e m b er 2 0 1 7. 
H e h as tr ai n e d o v er 1 5 0 r es e arc h ers, h a s o v er 4 5 0 p u blis h e d p a p ers a n d m a n uscri pts a n d h as l o n g b e e n s u p p ort e d b y 
t h e N ati o n al I nstit ut es of H e alt h a n d ot h er n o n- pr ofit a n d f or- pr ofit a g e nci es f or his eff orts i n tr yi n g t o u n d erst a n d t h e 
d e v el o p m e nt, m at ur ati o n a n d a gi n g a n d r e g e n er ati o n of c artil a g e, b o n e, s ki n a n d ot h er m es e nc h y m al tiss u es a n d f or his 
pi o n e eri n g r es e arc h o n M es e nc h y m al St e m C ells ( M S Cs). 
 
N or m a S. K e n y o n, P h D , st u d y C o-I, is t h e M arti n Kl ei m a n Pr of ess or of S ur g er y, Micr o bi ol o g y a n d I m m u n ol o g y a n d 
Bi o m e dic al E n gi n e eri n g at t h e Di a b et es R es e arc h I nstit ut e, L e o n ar d M. Mill er Sc h o ol of M e dici n e, U ni v ersit y of Mi a mi. 
S h e is c urr e ntl y C hi ef I n n o v ati o n Offic er a n d Ex ec uti v e Dir e ct or of t h e W all ac e H. C o ult er C e nt er f or Tr a nsl ati o n al 
R es e arc h at t h e Mill er Sc h o ol of M e dici n e, as w ell as Vic e Pr o v ost f or I n n o v ati o n f or t h e U ni v ersit y of Mi a mi. Utilizi n g 
cli nic all y r el e v a nt tr a ns pl a nt m o d els, a n d as a c o-i n v esti g at or o n m ulti pl e cli nic al  tri als, Dr. K e n y o n a n d h er t e a m h a v e 
f oc us e d o n w a ys t o tr a ns pl a nt i ns uli n pr o d uci n g isl et c ells wit h o ut t h e n e e d f or lif e-l o n g a nti-r ej ecti o n dr u gs, i ncl u di n g 
t h e i nc or p or ati o n of st e m c ells i nt o tr a ns pl a nt pr ot oc ols t o e n h a nc e isl et e n gr aft m e nt a n d s ur vi v al. H er c urr e nt r es e arc h 
is f oc us e d o n t h e i m m u n o m o d ul at or y a n d gr aft pr o m oti ng eff ects of m es e nc h y m al st e m c ells o n all o gr afts.  
 
 
D a vi d B ai d al, M. D. st u d y C o-I, is Assist a nt Pr of ess or of M e dici n e at t h e U ni v ersit y of Mi a mi Mill er Sc h o ol of M e dici n e.  
Dr. B ai d al’s cli nic al tr ai ni n g a n d r es e arc h b ac k gr o u n d pr o v i d es hi m wit h u ni q u e q u alific ati o ns t o s ucc essf ull y c arr y o ut 
t h e g o als of t his cli nic al tri al. H e o bt ai n e d his M D at t h e U ni v ersi d a d C at ólic a S a nti a g o d e G u a y a q uil i n Ec u a d or i n 2 0 0 0 m 
a n d j oi n e d t h e Cli nic al Isl et Tr a ns pl a nt Pr o gr a m ( CI T P), D RI, U M as a p ost - d oct or al f ell o w i n 2 0 0 1. His r es p o nsi biliti es 
i ncl u d e d r ecr uit m e nt of i n di vi d u als wit h u nc o ntr oll e d T 1 D f or p artici p ati o n i n cli nic al tri als of isl et tr a ns pl a nt ati o n, 
m o nit ori n g a n d p erf or mi n g cli nic al e v al u ati o ns of p artici p a n ts p ost isl et tr a ns pl a nt ati o n, c o n d ucti n g m et a b olic t esti n g 
a n d e v al u ati n g m et a b olic m ar k ers of β -c ell f u ncti o n a n d r es er v e, as w ell as s e v er al r e g ul at or y acti viti es n a m el y, 
r e p orti n g of a d v ers e e v e nts t o r e g ul at or y e ntiti es, u p d ati n g st u d y pr ot oc ols a n d c o ns e nt f or ms, a n d c oll a b or ati o n i n t h e 
d e v el o p m e nt of y e arl y cli nic al r e p orts. H e s ucc essf ull y c o ll a b or at e d wit h ot h er r es e arc h ers a n d c h air e d t h e Tr a ns pl a nt 
C o or di n at ors/ D at a M a n a g ers c o m mitt e e f or t h e C oll a b or ati v e Isl et Tr a ns pl a nt R e gistr y ( CI T R) d uri n g its i n a u g ur al y e ar 
a n d w as a n acti v e m e m b er of s e v er al CI T R c o m mitt e es. H e c o m pl et e d his i nt er n al m e dici n e tr ai ni n g at J ac ks o n M e m ori al 
H os pit al, U M i n 2 0 1 2 a n d his cli n ic al a n d r es e arc h f ell o ws hi p i n E n d ocri n olo g y, Di a b et es a n d M et a b olis m at t h e B et h 
Isr a el D e ac o n ess M e dic al C e nt er a n d J osli n Di a b et es C e nt er, H ar v ar d Sc h o ol of M edici n e i n 2 0 1 5. H e r e-j oi n e d t h e C C T P, 
D RI, U M i n 2 0 1 7 a n d b ec a m e t h e C e nt er Dir ect or f or t h e Tri al N et  Cli nic al C e nt er at t h e D RI, U M. H e is c urr e ntl y i n v ol v e d 
wit h t h e m a n a g e m e nt of isl et tr a ns pl a nt r eci pi e nts, d e v e l o p m e nt of cli nic al tri als ai m e d at o pti mizi n g isl et 
tr a ns pl a nt ati o n a n d t esti n g n o v el c ell ul ar a n d i m m u n o m o d ul at or y t h er a pi es. C urr e nt cli nic al tri al b uil ds l o gic all y o n Dr. 
B ai d al’s pri or cli nic al a n d r es e arc h ex p e ri e nc e a n d h e is a n i nt e gr al m e m b er of t h e U M- D RI cli nic al r es e arc h t e a m. 
  
K h e mr aj Hir a ni, M P h ar m, P h D, M B A, R A C, CI P, C C R P : st u d y C o-I, is Assist a nt Pr of ess or of M e dici n e at t h e U ni v ersit y of 
Mi a mi Mill er Sc h o ol of M e dici n e. H e h as w or k e d f or m or e t h a n t hirt e e n y e ars t o pr o vi de g ui d a nc e a n d dir ecti o n f or 
cli nic al o p er ati o ns a n d r es e arc h w hil e p erf or mi n g o v ersi g ht f or r e g ul at or y c o m pli a nc e, q u alit y ass ur a nc e, a n d c o ntr ols. 
H e is r ec o g niz e d as a s u bj ect m att er ex p ert o n F D A a n d C F R r e g ul ati o ns r el at e d t o cli nic al tri als i n e n d ocri n ol o g y, 
HI V/ AI D S, c a nc er, C N S, Bi ol o gics, c ar di o v asc ul ar a n d i nf ecti o us  dis e as es, v acci n es, a n d s af et y u p d at es. T o d at e, h e h as 
b e e n p art of 5 0 0 + cli nic al tri als a n d h as b e e n a n i nt e gr al p art of i nt er disci pli n ar y t e a ms of cli nici a ns a n d r es e arc h st aff. 

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2 3 | P a g e  
 
 
C o nfi de ntial
  
His ar e as of ex p ertis e i ncl u d e: Cli nic al P h ar m ac y, P h ar m a c ol o g y, Dr u g D e v el o p m e nt, P h as e I t o I V Tri als, I C H/ G C P 
G ui d eli n es a n d F D A R e g ul ati o ns, R e g ul at or y D ossi er, M ulti pl e  T h er a p e utic Ar e as, D esi g n of R es e arc h Pr ot oc ol, R es e arc h 
C o m pli a nc e, D at a S af et y M o nit ori n g, H u m a n S u bj ect Pr ot ecti o n, P h ar m ac o vi gil a nc e, a n d Dr u g S af et y. F or o v er a d ec a d e, 
h e h as b e e n s er vi n g v ari o us c o m mitt e es pr ot ecti n g s u bj ects a n d o v ers e ei n g cli n ic al r es e arc h, i ncl u di n g I R Bs, D S M B, 
f e asi bilit y c o m mitt e e, dr u g s af et y etc. 
  
Xi u mi n X u, M Sc : st u d y C o-I, is t h e Dir ect or of t h e C hi n a- U S A C olla b or ati v e H u m a n Tr a ns pl a nt Pr o gr a m at t h e Di a b et es 
R es e arc h I nstit ut e ( D RI) at U ni v ersit y of  Mi a mi, L e o n ar d M. Mill er Sc h o ol of M e dici n e. S h e s er v es as Dir ect or of Q u alit y 
Ass ur a nc e a n d R e g ul at or y Aff airs Q u alit y C o ntr ol/ Ass ur a nc e of  c G M P C ell Pr oc essi n g a n d Tr a ns pl a nt C e nt er at F uz h o u 
G e n er al H os pit al, Xi a m e n U ni v ersit y, C hi n a.  S h e als o s er v e d as S u p er vis or of t h e st at e-lic e ns e d Cli nic al Fl o w C yt o m etr y 
L a b or at or y ( 2 0 0 4- 2 0 1 3). S h e h as m or e t h a n 2 5 y e ars of l a b or at or y ex p eri e nc e, pri m aril y i n h u m a n c ells a n d tiss u es 
pr oc essi n g, i ncl u di n g b ut n ot li mit e d t o h e m at o p oi etic c ells fr o m v ert e br al b o d y  m arr o w, m o biliz e d p eri p h er al bl o o d, 
c or d bl o o d, ili ac cr est as pir at es b o n e m arr o w; m es e nc h y m al st e m c ells fr o m f at, b o n e m arr o w, u m bilic al c or d, a n d 
pl ac e nt a; isl ets fr o m c a d a v eric p a ncr e as a n d a ut ol o g o us d o n ors. H er ar e a of i nt er est is tr a nsl ati o n al a n d p ot e nti al 
cli nic al a p plic ati o ns i n t h e fi el d of tr a ns pl a nt i m m u n ol o g y a n d r e g e n er ati v e m e dici n e. 
 
R o d olf o Al ej a n dr o, M D , st u d y C o-I, h as > 3 0 y e ars cli nic al tri al exp eri e nc e i n T 1 D i m m u n ot h er a pi es a n d isl et 
tr a ns pl a nt ati o n. W or ki n g cl os el y, t h e PI a n d C o- PI will ass ur e t h at all p ers o n n el i n v ol v e d i n t h e st u d y ar e a p pr o pri at el y 
tr ai n e d, t h e pr oj ect is i niti at e d a n d c o n d uct e d as o utli n e d i n t h e pr oj ect-s p ecific i nstit uti o n al S O Ps a n d a p plic a bl e 
r e g ul ati o ns. PI m e nt ors will s er v e as sci e ntific a d vis ors. R eg ul ar m e eti n gs will b e h el d o n r e g ul ar b asis as t h e pr oj ect 
d e v el o ps, t o d e al wit h pr o bl e ms as t h e y  aris e. St u d y PI, C o- PI a n d m e nt ors will ass ur e s m o ot h c o n d uct of t h e pr oj ect. 
  
A nt o ni o C. M artt os, M D,  st u d y C o-I, is Ass oci at e Pr of ess or of S ur g er y, Dir ect or of Gl o b al e- H e alt h/ Tr a u m a T el e m e dici n e, 
C o- Dir ect or of t h e Willi a m L e h m a n I nj ur y R es e arc h C e nt er, R y d er Tr a u m a C e nt er- J ac ks o n M e m ori al H os pit al - U ni v ersit y 
of Mi a mi. Dr. M artt os is a pi o n e er i n Tr a u m a T el e m e dici n e h a s b e e n i n v ol v e d i n n u m er o us stu di es a n d cli nic al acti viti es 
f or t h e D e p art m e nt of D ef e ns e, t h e U. S. D e p art m e nt of Stat e, a n d t h e Fl ori d a D e p art m e nt  of H e alt h.  H e cr e at e d a 
st at e wi d e Tr a u m a T el e m e dici n e N et w or k a n d r ec ei v e d t h e h e alt h d e p art m e nt’s O utst a n di n g L e a d ers hi p A w ar d a n d als o 
t h e First A n n u al St at e S ur g e o n G e n er al H e alt h I n n o v ati o n, Pre v e nti o n, a n d M a n a g e m e nt A w ar d f or t h es e eff orts. H e is 
als o d e e pl y i n v ol v e d i n d e v el o pi n g t el e m e dici n e s ol uti o ns t o  pr o vi d e ex p ert s u p p ort i n m ulti pl e tr a u m a e n vir o n m e nts, 
i ncl u di n g t h e R es uscit ati o n a n d I nt e nsi v e C ar e u nits, t h e o p er ati n g r o o m, pr e- h os pit al a n d m ass c as u alt y. H e l e d t h e 
T el e m e dici n e E d uc ati o n a n d A d vic e f or M ilit ar y M e dici n e ( T E A M M) pr oj ect, w hic h li n k e d t h e R y d er Tr a u m a C e nt er wit h 
t h e U. S. Air F orc e, a n d h as ex pl or e d t h e us e of t el e m e dici n e i n m ass c as u alt y ex ercis es wit h t h e U. S. Ar m y F or w ar d 
S ur gic al T e a ms, as w ell as i n ex ercis es c o n d uct e d at m ulti pl e h os pit als acr oss Fl ori d a.  M ost r ec e ntl y, Dr. M artt os h as 
cr e at e d a n u n p ar all el e d Gl o b al T el e m e dici n e pr o gr a m f u n d e d b y t h e D e p art m e nt of St at e, t o pr o vi d e tr a u m a 
t el e m e dici n e s u p p ort s er vic es i n Ir a q. T h e pr o gr a m h as r ec ei v e d n ati o n al att e nti o n a n d is n o w c o nsi d er e d t h e g ol d 
st a n d ar d f or s uc h pr o gr a ms. Dr. M artt os is t h e Pr esi d e nt El ect of t h e P a n a m eric a n Tr a u m a S oci et y a n d c urr e ntl y 
l a u nc h e d 2 M e dic al si m ul ati o ns c o urs es t h at h a v e b e e n i m pl e m e nt e d ar o u n d t h e w orl d " Critic al D ecisi o ns i n Tr a u m a 
a n d Critic al D ecisi o ns i n M e dic al E m er g e nci es". H e is a f ull Ti m e Tr a u m a S ur g e o n d al Critic al C ar e P h ysici a n at U ni v ersit y 
of Mi a mi/J ac ks o n M e m ori al H os pit al s yst e m.  A n dr e w P ast e ws ki, M D,  is c urr e ntl y t h e M e dic al Dir ect or of t h e I C U 
at J ac ks o n S o ut h M e dic al C e nt er.  H e gr a d u at e d fr o m R oss U ni v ersit y Sc h o ol  of M e dici n e i n 2 0 0 1 a n d 
c o m pl et e d his i nt er n al m e dici n e r esi d e nc y a n d f ell o ws hi p tr ai ni n g i n P ul m o n ar y/ Critic al C ar e M e dici n e at 
M ai m o ni d es M e dic al C e nt er i n Br o o kl y n, N Y i n 2 0 0 7.   H e j oi n e d his p art n er, Ric h ar d Pr a g er, a n d t h e y h a v e 
b e e n m a n a gi n g t h e I C U at J ac ks o n S o ut h si nc e 2 0 0 7.  I n 2 0 2 1 Dr. P ast e ws ki’s  t e a m will b e m a n a gi n g t h e I C U at 
t h e n e w J ac ks o n W est.  Dr. P ast e ws ki is als o t h e C h air m a n of t h e C P R C o m mitt e e as w ell as t h e Dir ect or of 
R es pir at or y at J ac ks o n S o ut h.  
 
E nri q u e Gi nz b ur g, M D , is Tr a u m a M e dic al Dir ect or at R y d er Tr a u m a c e nt er at J ac ks o n S o ut h M e dic al C e nt er a n d 
Pr of ess or of S ur g er y i n t h e U ni v ersit y of Mi a mi Mill er Sc h o ol  of M e dici n e. H e gr a d u at e d fr o m U ni v ersit y of C alif or ni a 
wit h a B A d e gr e e a n d w e nt o n t o gr a d u at e fr o m U ni v ersit y  of Mi a mi Sc h o ol of M e dici n e i n 1 9 8 5. H e fi nis h e d his 
r esi d e nc y i n S ur g er y at J ac ks o n M e m ori al H os pit al a n d w e nt o n t o fi nis h his f ell o ws hi p i n V asc ul ar S ur g er y wit h V asc ul ar 

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C o nfi de ntial
  
S ur g e o ns of C e ntr al O hi o. H e r et ur n e d t o U ni v ersit y of Mi a mi i n 1 9 9 4 a n d h as r e m ai n e d o n st aff. H e is d o u bl e b o ar d 
c ertifi e d i n G e n er al S ur g er y a n d S ur gic al Critic al C ar e. H e h a s s er v e d as Vic e C h air of t h e Fl ori d a B o ar d of M e dici n e, 
H e alt h a d vis or t o t h e P a n A m eric a n D e v el o p e m e nt F o u n d ati o n, B o ar d of Pr oj ect M e dis h ar e, Vic e C h air F u n d aci o n 
Tr a u m a i n B u e n os Air es,  B o ar d of Dir ect ors f or U ni v ersit y  of Mi a mi M e dic al Gr o u p, B o ar d of Dir ect ors W est er n Tr a u m a 
Ass oci ati o n, a n d m e m b er of t h e U ni v ersit y of Mi a mi F ac ult y S e n at e. H e h as b e e n pri nci pl e i n v esti g at or i n m ulti pl e 
r es e arc h pr oj ects a n d a d vis or t o S a n ofi A v e ntis a n d  Grif ols P h ar m a. H e is ext e nsi v el y p u blis h e d i n p e er r e vi e w j o ur n als 
a n d m ulti pl e c h a pt ers i n t h e fi el d of S ur g er y.  
  
Mic h a el J. P ai d as, M D,  st u d y C o-I, Pr of ess or a n d C h air, D e p art m e nt of O bst etrics, G y n ec ol o g y & R e pr o d ucti v e Sci e nc es 
at t h e U ni v ersit y of Mi a mi Mill er Sc h o ol of M e dici n e, a n d C hi e f of S er vic e at U ni v ersit y H e alt h T o w er a n d J ac ks o n H e alt h 
S yst e m. As a m at er n al f et al m e dici n e cli nici a n sci e ntist, Dr . P ai d as’ c ar e er i n m e dici n e h as f oc us e d i n t h e fi el ds of 
r e pr o d ucti o n,  p eri n at al  m e dici n e  a n d  h e m ost asis,  wit h  activiti es  s p a n ni n g  p ati e nt  c ar e ,  tr a nsl ati o n al  r es e arc h  a n d  
cli nic al tri als. H e is r ec o g niz e d as i n t er n ati o n al a ut h orit y i n h e m ost asis dis or ders a n d w o m e n’s h e alt h. H e h as a ut h or e d 
or c o- a ut h or e d 1 3 4 p e er r e vi e w e d articl es. His r es e arc h h as b e e n s u p p ort e d b y f e d er al a n d n o n-f e d er al a g e nci es, 
i ncl u di n g t h e NI H. F or w ell o v er 1 9 y e ars, Dr. P ai d as h as ass u m e d a l e a di n g r ol e i n r es e arc h c o nc er ni n g t h e di a g n ostic 
a n d  t h er a p e utic  a p plic ati o ns  i n  ci vili a n  a n d  milit ar y  s etti n g s  of  Pr e-I m pl a nt ati o n  F act or  ( PI F),  w hic h  p oss ess es  k e y  
i m m u n e  m o d ul at or y,  n e ur o pr ot ecti v e  &  n e ur o-r e g e n er ati v e  pr o p erti es  i n  pr e g n a nc y  a n d  n o n- pr e g n a nc y  r el at e d  
c o n diti o ns. Dr. P ai d as w as Pri nci p al I n v esti g at or of a n NI H gr a nt e v al u ati n g PI F as a tr e at m e nt f or r a di ati o n i nj ur y fr o m 
t h e N ati o n al I nstit ut e of All er g y & I nf ecti o us Dis e as e, a n d c urr e ntl y is Pri nci p al I n v esti g at or at U M M S O M f or a n NI C H D 
f u n d e d gr a nt e v al u ati n g PI F i n a d diti o n t o h y p ot h er mi a t o tr e at n e o n at al br ai n i nj ur y. Dr. P ai d as h as s er v e d as Pri nci p al 
I n v esti g at or a n d St e eri n g C o m mitt e e C h air of a 2 3 sit e r a n d omiz e d cli nic al tri al i n pr et er m pr e ecl a m psi a, a n d h a v e 
p artici p at e d i n m ulti pl e st e eri n g c o m mitt e es a n d NI H r e vi e w p a n els. 
  
J o N ell E. P ott er, P h D, st u d y C o-I, is Pr of ess or of Cli nic al O bst etrics a n d G y n ec ol o g y at t h e U ni v ersit y of Mi a mi, Mill er 
Sc h o ol of M e dici n e, wit h j oi nt a p p oi nt m e nts i n t h e D e p art m e nt  of P e di atrics a n d Sc h o ol of N ursi n g. S h e als o s er v es as 
t h e Vic e C h air f or R e pr o d ucti v e Sci e nc es, a n d C hi ef of t h e W o m e n’s HI V S er vic e at J ac ks o n H e alt h S yst e m. S h e h as 
s er v e d as a n I n v esti g at or o n m ulti pl e, f e d er all y f u n d e d r es e arc h pr oj ects a n d h as a ut h or e d d oz e ns of m a n uscri pts, b o o k 
c h a pt ers, a n d pr es e nt ati o ns at n ati o n al a n d i nt er n ati o n al m e eti n gs. I n h er r ol e as Vic e C h air f or R e pr o d ucti v e Sci e nc es, 
s h e will assist t h e PI a n d pr oj ect t e a m wit h s p eci m e n c oll ecti o n a n d ot h er as p ects of t his tri al t o e ns ur e t h e g o als of t h e 
pr oj ect ar e m et.   
  
Ji a n mi n g T a n, M D, P h D, st u d y C o-I, is Pr of ess or of S ur g er y at F uz h o u G en er al H os pit al, Xi a m e n U n i v ersit y, C hi n a. Dr. T a n 
s er v es as Vic e Pr esi d e nt of F uz h o u G en er al H os pit al, Xi a m e n U ni v ersit y a n d Di r ect or of C ell a n d Or g a n Tr a ns pl a nt 
I nstit uti o n of t h e PL A. Dr. T a n als o s er v es as Dir ect or of t h e F uji a n K e y L a b or at or y of Tr a ns pl a nt Bi ol o g y a n d Dir ect or of 
D e p art m e nt of Ur ol o g y of F uz h o u G e n er al H os pit al. Dr. T a n is a f o u n di n g m e m b er of T h e C ur e Alli a nc e, a n d is a w orl d-
r e n o w n e d s ur g e o n sci e ntist wit h o v er 3 0 y e ars of ex p eri e nc e f oc usi n g o n tr a nsl ati o n al a n d cli nic al r es e arc h pr oj ects i n 
t h e fi el d of tr a ns pl a nt i m m u n o bi ol o g y, a ut oi m m u nit y, i m mu n ot h er a p y, r e g e n er ati v e m e dici n e, st e m c ells, a n d tiss u e 
e n gi n e eri n g. I n r ec e nt y e ars, Dr. T a n h as l e d a n u m b er of cli n ic al tri als o n t h e us e of U C- M S C c ell ul ar t h er a pi es i n or g a n 
tr a ns pl a nt ati o n, a ut oi m m u nit y, di a b et es m ellit us, a n d is n o w l e a di n g pil ot eff orts of U C- M S C i nf usi o n i n s e v er e c as es of 
C O VI D- 1 9.  
  
S h ari M essi n g er C a y et a n o, M E, P h D, st u d y C o-I, is t h e Dir ect or of t h e Bi ost atistics, E pi d e mi ol o g y a n d R es e arc h D esi g n 
C o m p o n e nt of t h e Mi a mi Cli nic al a n d Tr a nsl ati o n al Sci e nc es I nst it ut e ( C T SI). S h e is a T e n ur e d Pr of ess or i n t h e Di visi o n of 
Bi ost atistics, D e p art m e nt P u blic H e alt h Sci e nc es of t h e Mill er Sc h o ol of M e dici n e, a n d Dir ect or of t h e U ni v ersit y of 
Mi a mi Bi ost atistics C oll a b or ati o n a n d C o ns ulti n g C or e ( B C C C).  S h e h as c oll a b or at e d ext e nsi v el y wit h r es e arc h 
i n v esti g ati o ns wit hi n t h e Di a b et es R es e arc h I nstit ut e a n d Dr u g A b us e a n d Ai ds R es e arc h C e nt er. Dr. M essi n g er h as 
ext e nsi v e k n o wl e d g e a n d ex p eri e nc e i n a p plic ati o n of a p pr o pri at e st atistic al m et h o d ol o gi es a n d a m r es p o nsi bl e f or 
o v ers e ei n g t h e bi ost atistics s u p p ort f or b e nc h t o b e dsi d e tr a nsl ati o n i n m y r ol e as Dir ect or of t h e B C C C w h er e I l e a d all 
c oll a b or ati o n a n d c o ns ulti n g acti viti es pr o vi d e d b y M S a n d P h D l e v el B C C C st aff st atistici a ns. T h e m e m b ers of t h e B C C C 
c o v er a wi d e r a n g e of i nt er ests a n d st atistic al ex p ertis e a n d h a v e c o ns ulti n g ex p eri e nc e i n a v ari et y of s u bj ect m att er 
ar e as. A d diti o n all y, s h e is r es p o nsi bl e f or t h e d e v el o p m e nt a n d i m pl e m e nt ati o n of e d uc ati o n pr o gr a ms s uc h as t ut ori als, 

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cli nics, a n d w or ks h o ps c o v eri n g t o pics i n Bi ost atistics f or b ot h t h e B C C C st aff as w ell as Cli nic al a n d Tr a nsl ati o n al 
I n v esti g at ors. I t e ac h c o urs es a n d a d vis e M S a n d P h. D. stu d e nts i n Bi ost atistics. S h e h as ext e nsi v e k n o wl e d g e a n d 
ex p eri e nc e i n t h e d e v el o p m e nt, a p plic ati o n, a n d e d uc ati o n of a p pr o pri at e st atistic al m et h o d ol o g y f or t h e a n al ysis of 
cli nic al a n d tr a nsl ati o n al i n v esti g ati o ns at e v er y st a g e of r es e arc h. 
 
Lis a E. R af ki n, M S, R D, C D E, C C R C st u d y C o-I, is a R es e arc h Assist a nt Pr of ess or at t h e U ni v ersit y of Mi a mi Sc h o ol of 
M e dici n e, a n d h as b e e n i n v ol v e d i n t h e c o or di n ati o n a n d o v ersi g ht of m ulti-sit e t y p e 1 di a b et es pr e v e nti o n tri als f or 
o v er 2 5 y e ars. S h e s er v e d as C o- Dir ect or f or t h e Di a b et es Pr e v e nti o n Tri al – t y p e 1 ( D P T- 1)  fr o m 1 9 9 3- 2 0 0 1  a n d si nc e 
2 0 0 2 as Ass oci at e C h air f or Cli nic al C o or di n ati o n f or T y p e 1 Di a b et es Tri al N et.  S h e h as ext e nsi v e ex p eri e nc e i n 
c o or di n ati n g cli nic al r es e arc h n et w or ks,  pr o vi d es dir ecti o n a n d ex p ertis e i n t h e ar e a of i nf or m e d c o ns e nt,  a n d h as 
w or k e d o n d e v el o p m e nt of  m or e t h a n 3 0 T 1 D di a b et es pr e v e nti o n a n d n e w o ns et cli nic al tri als, as w ell as r el at e d 
a ncill ar y st u di es i ncl u di n g Dri e d Bl o o d S p ot a n d C a pill ar y Bl o o d S a m pli n g f or a ut o a n ti b o d y t esti n g t o d et er mi n e ris k f or 
T y p e 1 di a b et es. S h e w as i nt e gr all y i n v ol v e d i n est a blis hi n g a C e ntr al I R B f or Tri al N et at t h e U ni v ersit y of Mi a mi Sc h o ol of 
M e dici n e w hic h h el p e d  i m pr o v e n et w or k- wi d e effici e nci es wit h  o bt ai ni n g cli nic al tri al a p pr o v al f or Tri al N et  pr ot oc ols. 
 
R aff a ell a P o g gi oli, M D , st u d y C o-I, Gr a d u at e d i n It al y fr o m t h e U ni v ersit y of B ol o g n a M e dic al Sc h o ol i n 1 9 9 4 wit h a 
s p eci alt y d e gr e e i n E n d ocri n ol o g y, Di a b etes a n d M et a b olis m; W or k e d as a sci e nt ist at t h e U ni v ersit y of Mi a mi f or 1 2 
y e ars;  C o m pl et e d  a Cli nic al f ell o ws hi p i n E n d ocri n ol o g y Di a b et es a n d M et a b olis m fr o m t h e U ni v ersit y of Mi a mi Mill er 
sc h o ol of M e dici n e i n 2 0 1 2; Ac q uir e d ex p eri e nc e i n cli nic al  pr actic e i n t h e fi el d of o b esit y, n utriti o n a n d m et a b olic 
dis e as es; Dr. P o g gi oli h as r ec e ntl y r ej oi n e d t h e U ni v ersit y of Mi a mi Di a b et es R es e arc h I nstit ut e t o c o nti n u e h er c ar e er as 
a p h ysici a n sci e ntist; Dr. P o g gi oli h as si g nific a nt ex p eri e nc e i n cli nic al a n d tr a nsl ati o n al r es e arc h i n t h e fi el d of Di a b et es 
a n d isl et tr a ns pl a nt ati o n a n d will b e R es p o nsi bl e f or assisti n g i n  t h e c oll ecti o n/ a n al ysis of  d at a fr o m D RI cli nic al tri als. 
 
Cli nic al Tri al D esi g n 
S u bj ect S el ecti o n 
T h e pr o p os e d tri al is a c o ntr oll e d, r a n d o miz e d, d o u bl e bli n d cli n ic al tri al t o e v al u at e t h e s af et y a n d ex pl or e effic ac y of 
U C- M S C t h er a p y i n a d ult s u bj ects wit h C O VI D- 1 9. W e will e nr oll t w e nt y-f o ur ( n = 2 4) a d ul t s u bj ects di a g n os e d wit h 
C O VI D- 1 9.   S u bj ects  will  b e  r a n d o miz e d  i nt o  t w o  gr o u ps :  tr e at m e nt  ( n = 1 2)  a n d  c o ntr ol  ( n = 1 2).  T h e  Bi ost atistics  
C oll a b or ati o n a n d C o ns ulti n g C or e, a s h ar e d r es o urc e of t h e U ni v ersit y of Mi a mi Cli nic al a n d Tr a nsl ati o n al Sci e nc es 
I nstit ut e l e a d b y Dr. M essi n g er, h as g en er at e d si m pl e 1- 1, str atifi e d r a n d o miz ati o n sc h e m es a n d pr o vi d e d tr e at m e nt 
assi g n m e nts as p ati e nts ar e e nr oll e d i nt o t h e tri al.   Aft er eli gi bilit y is d et er mi n e d a nd p ati e nt is e nr oll e d, tr e at m e nt 
assi g n m e nt will b e pr o vi d e d acc or di n g t o t h e pr e- g e n er at e d str a tifi e d lists. T h e r a n d o miz ati o n t a bl es will b e m ai nt ai n e d 
i n t h e b ox d u e t o c o vi d- 1 9 s oci al dist a nci n g a n d w or k fr o m h o m e of s e v er al st aff. A n offici al c o p y will b e pl ac e d at t h e 
offic e of t h e Dir ect or of t h e c G M P f acili t y ( Di a b et es R es e arc h I nstit ut e, R o o m # 4 0 0 6). 
 
I ncl usi o n Crit eri a 
P ati e nts ≥ 1 8 y e ars ol d di a g n os e d wit h C O VI D- 1 9 ( as e v al u at e d b y P CR t est c o nfir mi n g i nf ecti o n wit h S A R S- C o V- 2) will b e 
eli gi bl e f or i ncl usi o n if t h e y m e et all of  t h e b el o w crit eri a. I ncl usi o n crit eri a m ust all b e pr es e nt wit hi n a 2 4- h o ur ti m e 
p eri o d at t h e ti m e of e nr oll m e nt: 
1.  P ati e nt c urr e ntl y h os pit aliz e d 
2.  A g e d ≥ 1 8 y e ars 
3.  Willi n g a n d a bl e t o pr o vi d e writt e n i nf o r m e d c o ns e nt, or wit h a l e g al r e pr es e nt ati v e w h o c a n pr o vi d e i nf or m e d 
c o ns e nt 
4.  P eri p h er al c a pill ar y ox y g e n s at ur ati o n ( S p O 2) ≤ 9 4 % at r o o m air, or r e q uiri n g s u p pl e m e nt al ox y g e n at scr e e ni n g 
5.  P a O 2/ Fi O2 r ati o < 3 0 0 m m H g 
6.  Bil at er al i nfiltr at es o n fr o nt al c h est r a di o gr a p h or bil at er al gr o u n d gl ass o p acit i es o n a c h est C T sc a n 
 

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Excl usi o n Crit eri a 
1.  P a O 2/ Fi O2 ≥ 3 0 0 at t h e ti m e of e nr oll m e nt 
2.  A pr e vi o us M S C i nf usi o n n ot r el at e d t o t his tri al  
3.  Hist or y of P ul m o n ar y H y p ert e nsi o n ( W H O Cl ass III/I V) 
4.  Cli nic al e vi d e nc e of l eft atri al h y p ert e n si o n or d ec o m p e ns at e d l eft h e art f ail ur e. 
5.  Pr e g n a nt or l act ati n g p ati e nt 
6.  U nst a bl e arr h yt h mi a  
7.  P ati e nts wit h pr e vi o us l u n g tr a ns pl a nt 
8.  P ati e nts c urr e ntl y r ec ei vi n g c hr o nic di al ysis  
9.  P ati e nts c urr e ntl y r ec ei vi n g Extr ac or p or e al M e m br a n e Ox y g e n ati o n ( E C M O)  
1 0.   E vi d e nc e of a n y acti v e m ali g n a nc y ( exc e pt n o n- m el a n o m a s ki n c a nc er) 
1 1.  A n y ot h er irr e v ersi bl e dis e as e or c o n diti o n f or w hic h 6- m o nt h m ort alit y is esti m at e d t o b e gr e at er t h a n 5 0 % 
1 2.  M o d er at e t o s e v er e li v er dis e as e ( A S T a n d AL T > 5 X UL N)  
1 3.  S e v er e c hr o nic r es pir at or y dis e as e wit h a P a C O 2 > 5 0 m m H g or t h e us e of h o m e ox y g e n 
1 4.  B as eli n e Q T pr ol o n g ati o n 
1 5.  M ori b u n d p ati e nt n ot ex p ect e d t o s ur vi v e > 2 4 h o urs  
 
 
 
Pl e as e n ot e t h at di p h e n h y dr a mi n e, h y dr ox yc hl or o q ui n e, a n d az it hr o m yci n all pr ol o n g t h e c ar di ac Q T i nt er v al, i ncr e asi n g 
ris k of f at al c ar di ac arr h yt h mi a. T h er ef or e, i n s e v er el y-ill s u bjects r ec ei vi n g m ulti pl e dr u gs t h at pr ol o n g Q T i nt er v als, t h e 
PI will c o nsi d er c as e- b y-c as e a dj u dic ati o n f or b e n e fit-ris k r ati o a n d cl os e c ar di o v asc ul ar m o nit ori n g. 
 
S u bj ects m e eti n g eli gi bilit y crit eri a w h o c o ns e nt t o st u d y p artici p ati o n will b e e nr oll e d i n t h e st u d y. F or e ac h s u bj ect, 
st u d y i d e ntific ati o n n u m b er a n d p artici p a nt’s n a m e will b e e nt er e d i nt o t h e st u d y l o g. Eli g i bl e p artici p a nts w h o h a v e 
si g n e d writt e n i nf or m e d c o ns e nt will r ec ei v e st u d y t h er a p y wit hi n 2 4 h o urs of st u d y e nr oll m e nt, will b e f oll o w e d f or 9 0 
d a ys f oll o wi n g tr e at m e nt.  
 
St u dy E n d p oi nts : 
T h e o utc o m es ar e i n li n e wit h t h os e fr o m o n g oi n g cli nic al tri als of M S C- b as e d t h er a p y f or A R D S. F urt h er m or e, t h e y ali g n 
wit h c urr e nt tri als f or C O VI D- 1 9 p ati e nts wit h s ec o n d ar y r es pir at or y c o m plic ati o ns i ncl u di n g ALI a n d A R D S. 
 
Pri m ary E n d p oi nts: 
S af et y, d efi n e d b y t h e occ urr e nc e of Pr e-s p ecifi e d I n f usi o n Ass oci at e d A d v ers e e v e nts aft er i nf usi o n. 
 A n y of t h e f oll o wi n g occ urri n g wit hi n 6 h p ost i nf usi o n: 
1.  A d diti o n of a d diti o n al v as o pr ess or a g e nts or a n i ncr e as e i n v as o pr ess or d os e gr e at er t h a n or e q u al t o t h e 
f oll o wi n g: 
o  N or e pi n e p hri n e: 1 0 μ g p er mi n 
o  P h e n yl e p hri n e: 1 0 0 μ g p er mi n 
o  D o p a mi n e: 1 0 μ g/ k g p er mi n 
o  E pi n e p hri n e: 1 0 μ g p er mi n  
 

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2. I n p ati e nts r ec ei vi n g m ec h a nic al  v e ntil ati o n: w ors e ni n g h y p ox e mi a, as ass ess e d b y a r e q uir e m e nt f or a n 
i ncr e as e of P E E P b y 5 c m H 2 O o v er b as eli n e, or r e q uire m e nt of a p erc e nt a g e i ncr e as e i n Fi O 2 of > 2 0 % fr o m 
b as eli n e.  
 
3. I n p ati e nts r ec ei vi n g hi g h fl o w ox y g e n t h er a p y:  w ors e ni n g h y p ox e mi a, as i n dic at e d b y r e q uir e m e nt of 
i nt u b ati o n a n d m ec h a nic al v e ntil ati o n.  
 
4. N e w c ar di ac arr h yt h mi a  r e q uiri n g c ar di o v ersi o n  
 
5. N e w v e ntric ul ar t ac h yc ar di a, v e nt ric ul ar fi brill ati o n, or as yst ol e  
 
6. A cli nic al sc e n ari o c o nsist e nt wit h tr a nsf usi o n i nc o m p ati bilit y or tr a nsf usi o n-r el at e d i nf ecti o n  
  
A n y of t h e f oll o wi n g occ urri n g wit hi n 2 4 h p ost i nf usi o n: C ar di ac arr est or d e at h. 
 
I nci d e nc e of S e v er e A d v ers e E v e nts ( S A Es) [ Ti m e Fra m e: I n v esti g at ors will c o n d uct ass ess m e nts f or t h e 
pr es e nc e of a n y a d v ers e e v e nts ( A E) fr o m e nr oll m e nt t hr o u g h st u d y d a y 9 0 or h os pit al disc h ar g e, w hic h e v er 
occ urs first]. 
  
S ec o n d ary E n d p oi nts: 
Ex pl or at or y effic ac y, d efi n e d b y: 
1. Cli nic al o utc o m es t h at i ncl u d e 
•  
S ur vi v al at d a y 2 8  
•  
S ur vi v al at d a y 6 0  
•  
Ti m e t o h os pit al disc h ar g e  
•  
V e ntil at or-fr e e d a ys  
•  
Ox y g e n ati o n i n dic es:  
I n p ati e nts r ec ei vi n g Hi g h Fl o w Ox y g e n t h er a p y: R O X i n d ex d efi n e d as R O X = ( S p O 2/ Fi O 2)/r es pir at or y 
r at e ( R R) I n p ati e nts o n m ec h a nic al v e ntil ati o n: Ox y g e n ati o n I n d ex ( OI), d efi n e d as OI = ( Fi O 2 x 
M P A W)/ P a O 2; w h er e Fi O 2 = fr acti o n of i ns pir e d O 2 ; M P A W = M e a n air w a y press ur e ( v e ntil at or); a n d 
P a O 2 = p arti al pr ess ur e of ox y g e n i n art eri al bl o o d 
•  
Dri vi n g Pr ess ur e ( P pl at – P E E P) if a p plic a bl e a n d a v ail a bl e i n t h e el ectr o nic  m e dic al r ec or d c h arts 
•  
S O F A ( S e q u e nti al Or g a n F ail ur e Ass ess m e nt)  
•  
S m ell I d e ntific ati o n T est ( SI T) or olf act or y t esti n g  
 
2. L a b or at or y t esti n g:  
•  
C o m pl et e Bl o o d C o u nt ( C B C) wit h diff er e nti al  
•  
C o m pr e h e nsi v e M et a b olic P a n el ( M P)  
•  
C-r e acti v e pr ot ei n  
•  
A A/ E P A r ati o  
•  
D- di m er  
•  
2 5- O H Vit a mi n D l e v els  
•  
All o a nti b o di es ( P a n el R e acti v e A nti b o di es, P R A)  
•  
Vir al L o a d b y S A R S- C o V- 2 R T- P C R  
•  
S er ol o g y t esti n g f or S A R S- C o V- 2 I g G/I g M  
 

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3. M ec h a nistic st u di es m a y i ncl u d e 
•  
M ulti pl ex ELI S A ass essi n g of pl as m a I nfl a m m at or y p a n el ( # 4 0) of c yt o ki n es, c h e m o ki n es a n d gr o wt h f act ors    
•  
ELI S A ass ess m e nt of pl as m a l e v els of S 1 P a n d s P D-L 1  
•  
P B M C ass ess m e nt of T c ell p o p ul ati o ns a, i ncl u di n g:  
o  O v er acti v at e d c yt o ki n e-s ecr eti n g C X C R 3 + C D 4 + T c ells  
o  C X C R 3 + C D 8 + T c ells  
o  C X C R 3 + N K c ells  
o  C D 1 4 + C D 1 1c + C D 1 1 b mi d r e g ul at or y D C c ell p o p ul ati o n  
o  C D 4 + C D 2 5 + F O X P 3 + Tr e gs  
  
St u dy Pr oc e d ur es: St u dy d esi g n, i ncl u di n g t h e s e q u e nc e a n d ti mi n g of st u dy pr oc e d ur es   
 
T h e pr o p os e d tri al is a c o ntr oll e d, r a n d o miz e d d o u bl e- bli n d cli nic al tri al t o e v al u at e t h e s af et y a n d effic ac y of U C- M S C 
t h er a p y i n a d ult s u bj ects wit h s e v er e C O VI D- 1 9. S u bj ects q u alifi e d f or t h e st u d y a n d r a n d o miz e d t o t h e tr e at m e nt gr o u p 
will b e tr e at e d wit h t w o d os es of U C- M S C ( 1 0 0 ± 2 0 x 1 0 6 c ells/ d os e), t h us d os e m a y r a n g e fr o m 8 0- 1 2 0 milli o ns p er 
i nf usi o n), d eli v er e d I V. S u bj ect r a n d o miz e d t o t h e c o ntr ol gro u p will r ec ei v e t w o i nf usi o ns of v e hicl e, d eli v er e d I V. T h e 
first d os e will b e i nf us e d wit hi n 2 4 +/- 6 h o urs f oll o wi n g stu d y e nr oll m e nt. A s ec o n d d os e will b e a d mi nist er e d 7 2 +/- 6 
h o urs aft er t h e first i nf usi o n.  S u bj ects will b e e v al u at e d d a il y d uri n g t h e first 6 d a ys, t h e n at 1 4, 2 8, 6 0, a n d 9 0 d a ys 
f oll o wi n g e nr oll m e nt (s e e Sc h e d ul e of Ass ess m e nt f or ti m e win d o w d et ails). I n a d diti o n, s u bj ects will r ec ei v e d ail y 
f oll o w- u p fr o m I C U ex p erts u ntil h os pit al disc h ar g e. Ai m 1 will ass ess s af et y of U C- M S C st u d y t h er a p y, w hil e Ai m 2 will 
a d dr ess effic ac y. T o c o ntr ol f or v ari a bilit y i n st u d y t h er a p y, st u d y s u bj ects will b e tr e at e d wit h U C- M S Cs d eri v e d fr o m a 
si n gl e M C B (si n gl e U C s o urc e). T h e visits ar e s p ecifi e d i n d et ail i n t h e Sc h e d ul e of Ass ess m e nt. 
 
D ail y f oll o w- u p visits will b e c o n d uct e d u ntil h os pit al disc h ar g e b y t h e I C U st aff t o e ns ur e o pti m al b est s u p p orti v e c ar e 
b ot h all s u bj ects. Vit al si g ns, t e m p er at ur e, p uls e, bl o o d pr e ss ur e, r es pir at or y r at e, oxi m etr y or v e ntil at or d at a will b e 
c oll ect e d. 
 
Sc he d ule of Assess me nt 
 
Pr oce d ures  
Visit 1 
Scree ni n g/ E nr oll me nt/ B aseli ne 
D a y - 1 or 0  
Visit 2, D a y 
0  
or wit hi n 2 4 
+/- 6 h  fr o m 
e nr oll me nt  
Visit 
3   
D a y 
1 ± 
6 h  
Visit 
4  
D a y 
2 ± 
6 h  
Visit 
5  
D a y 
3 ± 
6 h  
Visit 
6  
D a y 
4 ± 
6 h  
Visit 
7  
D a y 
5 ± 
6 h  
Visit 
8  
D a y 
6 
± 6 h  
Visit 
9  
D a y 
1 4 ± 3 
d a ys  
Visit 
1 0  
D a y 
2 8 ± 3 
d a ys  
Visit 
1 1 
D a y 
6 0 
± 7 
d a ys  
Visit 
1 2 
D a y 
9 0 
± 7 
d a ys  
I nf or me d c o nse nt 
X   
   
   
   
   
   
   
   
   
   
   
  
De m o gr a p hics 9 
X  
   
   
   
   
   
   
   
   
   
   
  
Me dic al hist or y
9 
X  
   
   
   
   
   
   
X   
X   
X   
X   
X  
O x y ge n ati o n I n de x ( OI)  
X   
   
   
   
   
   
   
X   
X   
X   
   
  
Se q ue nti al Or g a n F ail ure Assess me nt 
( S O F A)  
X  
   
   
   
   
   
   
X   
X   
X   
   
  
S mell I de ntific ati o n Test ( SI T) or 
Olf act or y testi n g ( o pti o n al) 
 
   
   
   
   
   
   
   
( X)1   
( X)1 
 
( X)
1 
  
Arteri al Bl o o d G as ( A B G) 2 
X  
X   
X  
X  
X  
X   
X   
X   
X   
X   
   
  
Bl o o d c ollecti o n f or l a b or at or y testi n g: 
c yt o ki ne p a nel, P R A, A A/ E P A, 2 5 O H 
Vit a mi n D, i m m u ne cell p o p ul ati o ns, 
D- di mer, C R P. Tr o p o ni n I, fr o m 
me dic al rec or ds if a v ail a ble.
1 0 
X  
   
   
   
X   
   
   
X   
X   
X
   
  
Vir al L o a d b y S A R S- C o V- 2 R T- P C R 
X
 
 
 
 
 
 
 
 
 
 X
 
 
 
 
 
Ser ol o g y testi n g f or S A R S- C o V- 2 
I g G/I g M 
X
 
 
 
 
 
 
 
 
 X
 X
 
 
 
St a n d ar d of c are: C B C, B asic 
Met a b olic P a nel (if a v ail a ble)  
X  
X   
X   
X   
X   
X   
X   
X   
X   
X  
   
  
C hest r a di o gr a p h, C T sc a n, or 
ultr as o u n d  
X 3, 6  
 
 
  
  
  
   
   
  
Pre g n a nc y test ( w o me n wit h 
c hil d be ari n g p ote nti al, wit h o ut si g ns or 
c urre nt hist or y) (fr o m me dic al hist or y) 
X   
   
   
   
   
   
   
   
   
   
   
  
Re vie w of I ncl usi o n E xcl usi o n criteri a 
X   
   
   
   
   
   
   
   
   
   
   
  

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
2 9 | P a g e  
 
 
C o nfi de ntial
  
C o nc o mit a nt me dic ati o n re vie w 9 
X  
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X  
U C- M S C or ve hicle a d mi nistr ati o n 
(i ntr a ve n o us i nf usi o n)1 1 
  
X   
   
   
X   
   
   
   
   
   
   
  
A d verse e ve nt assess me nt  
   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X  
Assess me nt f or I nf usi o n Ass oci ate d 
A d verse e ve nts wit hi n 2 4 h o urs.  
   
X   
   
   
X   
   
   
   
   
   
   
  
M o nit ori n g f or V as o press or a ge nt 
a d diti o n  
  
X   
   
   
X   
   
   
   
   
   
   
  
M o nit ori n g f or 
arr h yt h mi a/t ac h yc ar di a/ 
fi brill ati o n/ as ystole/c ar di ac arrest 
  
X   
   
   
X   
   
   
   
   
   
   
  
M o nit ori n g f or tr a nsf usi o n 
i nc o m p ati bilit y/i nfecti o n   
   
X   
   
   
X   
   
   
   
   
   
   
  
 
M o nit ori n g f or Ve ntil at or nee d 
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
   
  
M o nit ori n g f or c ar di ac arrest or de at h 
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
   
  
S F 3 6 q u alit y of life He alt h s ur ve y 
   
   
   
   
   
   
   
   
 X4 
X
X   
X  
Vit al si g ns 5, p ulse o xi metr y 
 X 
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X 
D ail y pr o gress n otes 7 
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X 
 
1) O pti o n al, b ase d o n p atie nt c o n diti o n.  
2) if av ail a ble.  
3) Av ail a ble p ul m o n ary cli nic al i m a gi n g o bt ai ne d cl osest t o ti me of i nt u b ati o n will be use d as t he scree ni n g p ul m o n ary i m a gi n g.  
4) at or bef ore disc h ar ge fr o m t he H os pit al  
5) Vit al si g ns: te m per at ure, p ulse, bl o o d pr ess ure, res pir at ory r ate. W he n t he s u bjec t is o n ve ntil at or, o bt ai n ti d al v ol u me, Fi O 2, res pir at ory r ate, 
P E E P/ w he n t he s u bject is o n n as al c a n n ul a, o bt ai n O 2 fl o w r ate / w he n t he s u bject is o n ot her s u p ple me nt ary oxy ge n, o bt ai n Fi O 2 if av ail a ble, u ntil 
h os pit al disc h ar ge.  
6) After Visit 1, a d diti o n al c hest i m a gi n g m ay be perf or me d b ase d  o n cli nic al nee d, f oll o wi n g H os pit al cli nic al g ui deli nes f or t he tre at me nt of 
C O VI D- 1 9 p atie nts.   
7) Atte n di n g n ote d oc u me nte d d aily, if av ail a ble. 
8) S u bjects HI V res ults a n d st at us as well as  pre g n a ncy test res ults (if a p plic a ble/f or eli gi ble p atie nts) n ote d i n t he me dic al  rec or ds will be o bt ai ne d 
a n d d oc u me nte d i n t he st u dy rec or ds.  
9) O bt ai ne d fr o m Me dic al Rec or ds.  
1 0) Bl o o d c ollecti o n will be perf or me d u ntil disc h ar ge. 
1 1) Vit al si g ns as per st a n d ar d pr oce d ure per p atie nt severity a n d  per pr ocess of cli nic al site I C U C O VI D- 1 9 setti n gs (e. g. p ara meters like 
te m per at ure rec or de d less fre q ue ntly).  
 
B ec a us e olf act or y l oss ( a n os mi a) h as b e e n r e p ort e d as a c o m m o n pr o bl e m i n C O VI D- 1 9 p ati e nts, w e will als o i ncl u d e 
olf act or y t esti n g, t o i d e ntif y e vi d e nc e f or i m pr o v e m e nt i n M S C-tr e at e d s u bj ects. At pr es e nt, t h e m ec h a nis m of olf act or y 
l oss wit h C O VI D- 1 9 i nf ecti o n is u n k n o w n. Olf acti o n will b e m e asur e d usi n g t h e S m ell I d e ntific ati o n T est ( SI T, S e ns o nics, 
NJ). T h e SI T is a s elf- a d mi nist er e d 4 0-it e m t est i n v ol vi n g micr o e nc a ps ul at e d (scr atc h- a n d-s niff) o d ors wit h a f orc e d-
c h oic e d esi g n. T h er e ar e f o ur b o o kl ets wit h 1 0 q u esti o ns e ac h , as ki n g t h e s u bj ect t o i d e ntif y w hic h of f o ur a ns w ers b est 
d escri b e d  t h e  o d or.  T ot al  sc or es  ar e  c at e g oriz e d,  b as e d  o n  n or m ati v e  d at a,  as  n or m al ,  mil d  h y p os mi a,  m o d er at e  
h y p os mi a,  s e v er e  h y p os mi a,  t ot al  a n os mi a,  or  pr o b a bl e  m ali n g eri n g.  T h e  t est  w as  d e v el o p e d  at  U ni v ersit y  of  
P e n ns yl v a ni a as p art of a n NI H-f u n d e d pr o gr a m pr oj ect a n d is wi d el y us e d as a st a n d ar d ass ess m e nt of olf act or y 
f u ncti o n. ( R ef er e nc e: D ot y, R. L. et al. S m ell i d e ntific ati o n a bilit y: c h a n g e s wit h a g e. Sci e nc e 2 2 6, 1 4 4 1- 1 4 4 3 ( 1 9 8 4). As 
s p ecifi e d a b o v e i n t h e sc h e d ul e of ass ess m e nt, t his t est is o pti o n al b as e d o n su bj ect’s c o n diti o n a n d a bilit y t o p erf or m 
t his t est.  
 
V e ntil at or w e a ni n g a n d ass ess m e n t of r e a di n ess f or e xt u b ati o n 
I n or d er t o i m pr o v e c o nsist e nc y a m o n g st u d y sit es a n d pr o d uce r eli a bl y i nt er pr et a bl e r es ults,  st u d y s u bj ects will b e 
tr e at e d acc or di n g t o est a blis h e d b est pr actic e st a n d ar ds of c ar e, wit h p artic ul ar att e nti o n t o v e ntil at or w e a ni n g a n d 
ass ess m e nt of r e a di n ess f or ext u b ati o n. 
 
A. C o n d uct a s p o nt a n e o us br e at hi n g tri al d ail y w h e n: 
1. Fi O 2 ≤ 0. 4 0 a n d P E E P ≤ 8 O R Fi O 2 < 0. 5 0 a n d P E E P ≤ 5. 
2. P ati e nt h as acc e pt a bl e s p o nt a n e o us br e at hi n g eff orts. ( M a y d ecr e as e v e nt r at e b y 5 0 % f or 5 mi n ut es t o 
d et ect eff ort.) 
3. N o n e ur o m usc ul ar bl oc ki n g a g e nts or bl oc k a d e. 
B. S p o nt a n e o us br e at hi n g tri al: If a b o v e crit eri a ar e m et a n d s u bj ect h as b e e n i n t h e st u d y f or at l e ast 1 2 h o urs, i niti at e a 
tri al of u p t o 1 2 0 mi n ut es of s p o nt a n e o us br e at hi n g wit h Fi O 2 ≤ 0. 5 a n d P E E P ≤ 5: 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
3 0 | P a g e  
 
 
C o nfi de ntial
  
1. Pl ac e o n T- pi ec e, tr ac h c oll ar, or C P A P ≤ 5 c m H 2 O wit h P S ≤ 8 c m H 2 O 
2. Ass ess f or t ol er a nc e as b el o w f or u p t o t w o h o urs. 
a) S p O 2 ≥ 9 0: a n d/ or P a O 2 ≥ 6 0 m m H g 
b) S p o nt a n e o us V T ≥ 4 ml/ k g P B W 
c) R R ≤ 3 5/ mi n 
d) p H ≥ 7. 3 
e) N o r es pir at or y distr ess ( distr ess = 2 or m or e) 
( 1) H R > 1 2 0 % of b as eli n e 
M ar k e d acc ess or y m uscl e us e 
A b d o mi n al p ar a d ox 
Di a p h or esis 
M ar k e d d ys p n e a 
3. If n ot t ol er at e d r es u m e pr e- w e a ni n g s etti n gs. 
4. If t ol er at e d f or at l e ast 3 0 mi n ut es, c o nsi d er ext u b ati o n. 
  
T h e f oll o wi n g g ui d a nc e s er v es as r ef er e nc e: 
·         A R D S n et ( NI H N HL BI A R D S Cli nic al N et w or k) M ec h a nic al V e ntil ati o n Pr ot oc ol S u m m ar y 
( htt p:// w w w. ar ds n et. or g/fil es/ v e ntil at or _ pr ot oc ol _ 2 0 0 8- 0 7. p df) 
 
·         A m eric a n T h or acic S oci et y/ A m eric a n C oll e g e of C h est P h ysici a ns Cli nic al Pr actic e G ui d eli n e: Li b er ati o n fr o m 
M ec h a nic al V e ntil ati o n i n Crit ic all y Ill A d ults - Oct o b er 2 0 1 6 
 
htt ps:// w w w. atsj o ur n als. or g/ d oi/f ull/ 1 0. 1 1 6 4/rcc m. 2 0 1 6 1 0- 2 0 7 6 S T 
T h es e g ui d eli n es s h o ul d b e c o nsi d er e d as a p pr o pri at e i n t h e b est i nt er est of s u bj ects b as e d o n e ac h s u bj ect’s i n di vi d u al 
cli nic al circ u mst a nc es a n d t h e b est j u d g e m e nt  of t h eir tr e ati n g cli nic al c ar e t e a ms. 
 
 
St u dy d ur ati o n a n d n u m b er of st u dy visi ts r e q uir e d of r es e arc h p artici p a nts. 
 
T h e st u d y i n v ol v es a t ot al of 1 2 visits, wit h t h e l ast visit at 9 0  d a ys aft er st u d y e ntr y.  Visits will t a k e pl ac e at t h e cli nic al 
tri al sit e, at t h e H os pit al, or – f or t h os e p ati e nts disc h ar g e d fr o m t h e h os pit al pri or t o d a y 9 0- vi a T el e H e alt h or p h o n e 
c alls.  
 
Bli n di n g, i ncl u di n g j ustific ati o n f or bli n di n g or n ot bli n di n g t h e tri al, if a p plic a bl e. 
 
T h e c urr e nt st u d y s e e ks t o i d e ntif y a n “ effic ac y si g n al”, as w e ll as t o f urt h er d e v el o p a n u n d erst a n di n g of t h e s af et y a n d 
f e asi bilit y  of  t h e  pr oc e d ur e. F or  t his  e arl y  p h as e  st u d y,  d o u bl e  bli n d  tri als,  st u d y  i n v esti g at or  bli n d e d  t o  t h e  
tr e at m e nt/ v e hicl e assi g n m e nt will p erf or m cli nic al effic ac y ass ess m e nts. T h e c o ntr ol gr o u p will b e gi v e n a n i nf usi o n of 
Pl as m a-L yt e s u p pl e m e nt e d wit h 1 0 % H S A 7 0 U/ k g u nfr acti o n at e d H e p ari n, wit h i d e ntic al pr e- m e dic ati o n r e gi m e n as t h at 
i n t h e tr e at m e nt gr o u p. O nl y t h e q u alifi e d st aff i n v ol v e d i n r a n d o miz ati o n a n d pr e p ar ati o n of t h e i nf usi o ns will b e 
u n bli n d t o t h e assi g n m e nt.  
 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
3 1 | P a g e  
 
 
C o nfi de ntial
  
I n t h e e v e nt a d ecisi o n is r e q uir e d t o m a k e e m er g e nc y u n bli n di n g p ert ai ni n g t o t h e s af et y of t h e s u bj ects, s p o ns or-
i n v esti g at or will b e a v ail a bl e 2 4 X 7, a n d will m a k e a d et er mi n ati o n al o n g wit h st u d y i n v esti gat ors a n d tr e ati n g p h ysici a ns 
t o m a k e t h e fi n al d ecisi o n.  
 
J ustific ati o n of w hy p artici p a nts will n ot r ec eiv e r o uti n e c ar e or wi ll h av e c urr e nt t h er a py st o p p e d. 
 
P ati e nts e nr oll e d i nt o t h e st u d y p oss ess a dis e as e s ev erit y f or w hic h n o st a n d ar d of c ar e exists. P ati e nts will b e all o w e d 
t o c o nti n u e r ec ei vi n g r o uti n e s y m pt o m atic c ar e a n d c urr e nt t h er a p y. 
 
J ustific ati o n f or i ncl usi o n of a pl ac e b o or n o n-tr e at m e nt gr o u p. 
 
A c o ntr ol gr o u p will b e i ncl u d e d i n t h e c urr e nt st u d y. P ati e nts i n t his gr o u p will r ec ei v e a n i nf usi o n of Pl as m a-L yt e wit h 
e q u al d os es of H S A a n d h e p ari n as t h e tr e at m e nt gr o u p, as w ell as a n i d e ntic al pr e- m e dic ati o n r e gi m e n. All p ati e nts 
e nr oll e d i n t h e tri al will als o b e tr e at e d wit h st a n d ar d of c ar e. 
 
D efi niti o n of tr e at m e nt f ail ur e or p artici p a nt r e m ov al crit eri a. 
 
Tr e at m e nt f ail ur e will b e c h ar act eriz e d as l ac k of r es p o n s e o n q u alit ati v e a n d/ or q u a ntit ati v e p ar a m et ers ass ess e d. 
P artici p a nt will b e r e m o v e d fr o m t h e st u d y if t h e att e n di n g p h ysici a n b eli e v es it w o ul d b e i n t h e b est i nt er est of t h e 
s u bj ect t o h alt t h e tr e at m e nt. P artici p a nts ar e fr e e t o wit h dra w fr o m p artici p ati o n i n t h e st u d y at a n y ti m e u p o n r e q u est. 
 
A n i n v esti g at or m a y disc o nti n u e or wit h dr a w a p art ici p a nt fr o m t h e st u d y f or t h e f oll o wi n g r e as o ns: 
 
•  
Si g nific a nt st u d y i nt er v e nti o n n o n-c o m pli a nc e  
•  
If a n y cli nic al a d v ers e e v e nt ( A E), l a b or at or y a b n or m alit y, or ot h er m e dic al c o n diti o n or sit u ati o n occ urs s uc h 
t h at c o nti n u e d p artici p ati o n i n t h e st u d y w o ul d n ot b e i n t h e b est i nt er est of t h e p artici p a nt 
•  
Dis e as e pr o gr essi o n w hic h r e q uir es disc o nti n u ati o n of t h e st u d y i nt er v e nti o n 
•   
If  t h e  p artici p a nt  m e ets  a n  excl usi o n  crit eri o n  ( eit h e r  n e wl y  d e v el o p e d  or  n ot  pr e vi o usl y  r ec o g niz e d)  t h at  
pr ecl u d es f urt h er st u d y p artici p ati o n 
 
T h e r e as o n f or p artici p a nt disc o nti n u ati o n or wit h dr a w al fr o m t h e st u d y will b e r ec or d e d o n t h e C as e R e p ort F or m ( C R F). 
S u bj ects w h o si g n t h e i nf or m e d c o ns e nt f or m a n d ar e r a n d o miz e d b ut d o n ot r ec ei v e t h e st u d y i nt er v e nti o n m a y b e 
r e pl ac e d.  S u bj ects w h o si g n t h e i nf or me d c o ns e nt f or m, a n d ar e r a n d o miz e d a n d r ec ei v e t h e st u d y i nt er v e nti o n, a n d 
s u bs e q u e ntl y wit h dr a w, or ar e wit h dr a w n or disc o nti n u e d fr o m t h e st u d y, will n ot b e r e pl ac e d. 
 
D escri pti o n of w h at h a p p e ns t o p artici p a nts r ec eiv i n g t h er a py w h e n st u dy e n ds or if a p artici p a nt’s 
p artici p ati o n i n t h e st u dy e n ds pr e m at ur ely. 
 
P ati e nts ar e fr e e t o u n d er g o ot h er t h er a pi es w h e n t h e st u d y e n ds or if t h e p artici p a nt’s p artici p ati o n i n t h e st u d y e n ds 
pr e m at ur el y.  If t h er e is n o i m pr o v e m e nt i n t h e cli nic al p ar a m et ers wit h st u d y i nt er v e nti o n, p artici p a nts will b e gi v e n 
alt er n ati v es t o p artici p at e i n ot h er t h er a pi es t h at h a v e p ot e nti al f or i m pr o v e d b e n efits.  
 
S u bj ect P o p ul ati o n  
 
P ati e nt r ecr uit m e nt f or t h e cli nic al tri al will b e o p e n at t h e U ni v ersit y of Mi a mi H os pit al a n d J ac ks o n M e m ori al H os pit al 
a n d ot h er 5 c e nt ers acr oss t h e U S A.   D u e t o t h e n at ur e of t h e st u d y p o p ul ati o n, pr ox y/l e g all y a ut h oriz e d r e pr es e nt ati v e 
will b e all o w e d r e m ot el y vi a u ni v ersit y of  Mi a mi z o o m li n k t o pr o vi d e i nf or m e d c o ns e nt i n or d er t o a v oi d s pr e a d of 
c o vi d- 1 9 i nf ecti o n. N o discri mi n ati o n will b e m a d e as t o et h n icit y, a g e, i nc o m e, or e d uc ati o n if t h e f oll o wi n g crit eri a ar e 

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m et. T h er e will b e n o us e of t h e pr o d uc t f or e m er g e nc y us e i n t his cli nic al prot oc ol a n d a n y r e q u est f or e m er g e nc y us e 
will b e c o nsi d er e d/r e vi e w e d u n d er a s e p ar at e I N D fr o m t h e tr e ati n g p h ysici a n al o n g wit h t h e c o n diti o n of t h e p ati e nt. 
 
T o b e i ncl u d e d i n t h e st u d y t h e s u bj ect or t h e d esi g n e e ( e. g . L e g all y A ut h oriz e d R e pr es e nt ati v e eit h er i n p ers o n or 
r e m ot el y vi a z o o m li n k fr o m u ni v ersit y of Mi a mi) m ust c o m pl et el y u n d erst a n d t h e p ot e nti al ris ks a n d p ot e nti al b e n efit 
of p artici p ati n g i n t h e st u d y a n d c o ns e nt t o t his st u d y. All s u bj ects s h o ul d c o ns ult wit h t h eir p ers o n al p h ysici a n b ef or e 
a gr e ei n g t o p artici p at e i n t h e st u d y a n d b ef or e si g ni n g t h e i nf or m e d c o ns e nt f o r m. A n y q u esti o ns t h e p ati e nt h as will b e 
a ns w er e d b y t h e Pri nci p al I n v esti g at or v er b all y. Ot h er c o m m u nic ati o n wit h p ot e nti al s u bj ects will t a k e pl ac e b y e m ail 
a n d/ or f ax.  
 
Pl a ns t o m a k e t h e pr o d uct a v ail a bl e t o st u d y p artici p a nts aft er t h e st u d y c o ncl usi o n: T h e pr o d uct will n ot b e m a d e 
a v ail a bl e or pr o vi d e d t o s u bj ects aft er c o ncl usi o n of t h e st u d y.  
 
S u bj ects s h o ul d r e p ort a n y disc o mf orts, pr o bl e ms, or i nj uri es i m m e di at el y t o st u d y p h ysici a n. If i nj ur y occ urs as a r es ult 
of r el at e d pr oc e d ur es, i n m ost c as es, tr e at m e nt will b e a v ail a bl e a n d will b e bill e d t o s u bj ect’s i ns ur a nc e. H o w e v er, n o 
c o m p e ns ati o n will b e a v ail a bl e.   
 
S u bj ects m ust m e et all i ncl usi o n a n d excl usi o n crit eri a.  R es ults of all b as eli n e e v al u ati o ns, w hic h ass ur e t h at all i ncl usi o n 
a n d excl usi o n crit eri a h a v e b e e n s atisfi e d, m ust b e r e vi e w e d  b y t h e Pri nci p al I n v esti g at or or his/ h er d esi g n e e pri or t o 
e nr oll m e nt of t h at s u bj ect.  T h e s u bj ect m ust b e i nf or m e d a b o ut all as p ects of t h e st u d y a n d writt e n i nf or m e d c o ns e nt 
m ust b e o bt ai n e d fr o m t h e s u bj ect pri or t o st u d y pr oc e d ur es. 
I nv esti g ati o n al Pr o d uct  
 
T h e “ dr u g s u bst a nc e” f or t h e pr o p os e d cli nic al tri al will c o m pris e of U C- M S C d e ri v e d fr o m o n e h e alt h y d o n or.  B atc h 
r ec or ds a n d st erilit y a n d e n d ot oxi n t esti n g will b e p erf or m e d f or e ac h s a m pl e.   
 
U C- M S C  Fi n al Pr o d uct will b e m a n uf act ur e d  fr o m  a  pr e vi o usl y  est a blis h e d  U C- M S C  M C B. T h e M C B  a n d its s o urc e 
tiss u e  h a v e  b e e n  t est e d  acc or di n g  t o  t h e  a p plic a bl e  F D A  r e g ul ati o ns  a n d  A A B B  a n d  F A C T  st a n d ar ds  f or  c ell ul ar  
t h er a pi es. O n e vi al of U C- M S C M C B is t h a w e d a n d w as h e d i n D M E M  L o w Gl uc os e (L G, Gi bc o Lif e T ec h n ol o gi es, C arls b a d, 
C A) s u p pl e m e nt e d wit h 1 0 % Pl at el et G ol d ( Bi ol o gic al I n d ustri es,  Cr o m w ell, C T), 1x Gl ut a M A X (I n vitr o g e n, C arls b a d, C A), 
a n d 1x M E M- N E A A ( Gi bc o Lif e T ec h n ol o gi es, C arls b a d, C A). C ells ar e c o u nt e d t o d et er mi n e t ot al vi a bl e c ells a n d c ell 
vi a bilit y a n d pl at e d o nt o 5- 1 0 ( n = 5- 1 0) T- 2 2 5 c m 2  tiss u e c ult ur e fl as ks at a d e nsit y of 3, 5 0 0  c ells/c m2, a n d c ult ur e d i n 5 % 
C O 2 tiss u e c ult ur e i nc u b at ors, at 3 7° C, i n D M E M L G s u p pl e m e nt e d as i n dic at e d a b o v e, wit h m e di a c h a n g es e v er y 2 d a ys, 
t o ~ 8 0 % c o nfl u e nc e. St erilit y s a m pl e is c oll ect e d at t h e ti m e of h ar v est. C ells ar e h ar v est e d wit h Tr y pL E Ex pr ess E nz y m e 
( Gi bc o Lif e T ec h n ol o gi es, C arls b a d, C A) f or 3- 6 mi n ut es at 3 7° C, w as h e d a n d r e-s us p e n d e d i n c ult ur e m e di a, as d escri b e d 
a b o v e. S a m pl es ar e c oll ect e d t o ass ess t ot al vi a bl e c ells  a n d c ell vi a bilit y. C ells ar e c ult ur e d i n 1 5- 2 0 6 3 6 c m 2 Tiss u e 
C ult ur e  C h a m b ers  ( T h er m o Fis h er  Sci e ntific  W alt h a m,  M A)  f or  P 2,  a n d  u p  t o  2 4- 2 6  E as y Fill C ell  F act or y  4-l a y er  tiss u e  
c ult ur e c h a m b ers ( T h er m o Fis h er Sci e ntific, W alt h a m, M A) f or P 3, at a d e nsit y of 3, 5 0 0 c ells/c m 2 a n d ex p a n d e d t o 8 0 % 
c o nfl u e nc e at e ac h ex p a nsi o n. At t h e ti m e of e ac h h ar v est, c ells ar e c o u nt e d, vi a bilit y is ass ess e d b y Tr y p a n Bl u e d y e 
excl usi o n a n d st erilit y s a m pl es ar e c oll ect e d. D uri n g l ast h ar v est, i n a d diti o n t o t h e ass ess m e nt of t ot al vi a bl e c ells a n d 
c ell  vi a bilit y  b y Tr y p a n Bl u e,  s a m pl es ar e  c oll ect e d t o  ass e ss M yc o pl as m a b y P C R (c ells i n s p e nt m e di a). R es ulti n g c ell 
p ell et  is  r e-s us p e n d e d  i n  Cr y ost or ®  C S 1 0  ( Bi oLif e  S ol uti o n s,  B ot h ell,  W A)  s ol uti o n.  C ells  ar e  cr y o pr es er v e d  at  a  
c o nc e ntr ati o n of 2 0x 1 0 6 c ells / 1. 0 ml / cr y o vi al or 1 1 0x 1 06 c ells / 1 0- 1 5 ml / cr y o b a g.   
 
N ec ess ar y n u m b er of cr y o vi als/cr y o b a gs ( T h er m o Fis h er Sci e ntif ic, W alt h a m, M A) ar e pr e p ar e d b as e d o n t ot al vi a bl e c ell 
c o u nt, e ac h vi al is l a b el e d. L a b els are c o m pli a nt wit h I S B T 1 2 8, 2 1 C F R P art 1 2 7 1 a n d 2 1 C F R P art 6 1 0 r e q uir e m e nts. C ells 
ar e  cr y o pr es er v e d  usi n g  c o ntr oll e d  r at e  fr e ez er;  U C- M S C  Fi n al  Pr o d uct  vi als  ar e  st or e d  i n  Ultr a-L o w  T e m p er at ur e  
Fr e ez er/ v a p or i n  L N 2 st or a g e  t a n k at  >- 1 5 0° C.   T h e  u ni q u e  c h ar act eristic  of  t his  m a n uf act uri n g  pr oc ess  is  t h at  it  is  
c o m pl et e fr e e of x e n o g e n eic pr ot ei ns, w hic h is n ot c h ar act eristic of m ost M S C c ult ur e a n d d eri v ati o n s yst e ms. 

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T h e n ec ess ar y n u m b er of cr y o vi als/cr y o b a g s e g m e nts ar e r e m o v e d f or Fi n al Pr o d uct t esti n g w hic h i ncl u d es c ell d os e a n d 
c ell  vi a bilit y  b y  Tr y p a n  Bl u e  Excl usi o n  ( > 8 0 %),  c ell  p urit y  b y  Fl o w C yt o m etric a n al ysis  ( > 9 0 %  C D 9 0 +/ C D 1 0 5 +;  
C D 3 4 +/ C D 4 5 + < 5 %), E n d ot oxi n b y E n d ot oxi n P T S ® ( < 1. 6 5 E U/ m l), M yc o pl as m a b y P C R ( n e g ati v e, c ells r e-s us p e n d e d i n 
s p e nt m e di a is c oll ect e d d uri n g t h e l ast ( P 3) h ar v est), a n d 1 4- d a y st erilit y ( acc or di n g t o U S P < 7 1 >). U C- M S C Fi n al Pr o d uct 
is r el e as e d f or a d mi nistr ati o n/tr a ns pl a nt ( Tx) o nl y w h e n all pr o d uct r el e as e crit eri a ar e m et.   
 
W h e n t h e R e q u est f or Tx fr o m st u d y PI/ C o-I is r ec ei v e d, s uffici e nt n u m b er of cr y o vi als vi als c o nt ai ni n g 2 0x 1 0
6 c ells / ml 
or  1 1 0x 1 0 6 c ells  /  1 0- 1 5  ml  /  cr y o b a g  U C- M S C  Fi n al  Pr o d uct  t o  s atisf y  t h e  r e q uir e d  d os e  will  b e  r e m o v e d  fr o m  
L N 2 st or a g e,  q uic kl y  t h a w e d,  sl o wl y  dil ut e d  i n  4 0- 5 0  ml  of st eril e  Pl as m a-L yt e  ( U S P)  s u p pl e m e nt e d  wit h  1 0 %  H S A  
( U S P) a n d 7 0 U/ k g of u nfr acti o nat e d H e p ari n ( U S P), a n d tr a nsf err e d t o 3 0 0 ml tr a nsf er b a g ( F e n w al, L a k e Z uric h, IL) i n 
pr e p ar ati o n  f or  i nf usi o n.  T h e  fi n al  c ell  s us p e nsi o n  of  U C- M S C  T h a w e d  /  Dil ut e d  pr o d uct  (I P)  will  b e  r el e as e d  f or  
a d mi nistr ati o n  b as e d  o n  ass ess m e nt  of  c ell  d os e  a n d  c ell  vi a bilit y,  Gr a m  st ai n,  E n d ot oxi n,  FL O W  s urf ac e  m ar k er  
ass ess m e nt a n d 1 4- d a y st erilit y i m m e di at el y pri or t o tr a nsf er t o  t h e fi n al c o nt ai n er ( 3 0 0 ml tr a nsf er b a g). F o urt e e n- d a y 
st erilit y r es ults will s er v e as p ost- pr o d uct r el e as e crit eri a. T h e pr o d uct will b e pl ac e d i n a v ali d at e d tr a ns p ort c o nt ai n er 
fitt e d  wit h  t h e  c o nti n u o us  t e m p er at ur e  m o nit ori n g  d e vic e.  D et ail e d  S O Ps  h a v e  b e e n  i m pl e m e nt e d  f or  pr o d uct  
pr e p ar ati o n f or a d mi nistr ati o n a n d tr a ns p ort t o t h e cli nic al cit e  (I nt e nsi v e c ar e u nit, I C U). At t h e ti m e of st u d y i niti ati o n, 
I C U st aff will b e tr ai n e d o n h o w t o r ec ei v e t h e pr o d uct at t h e cli nic al sit e, r ec or ds r e q uir e m e nts a n d r et ur n of t h e 
tr a ns p ort c o nt ai n er, t e m p er at ur e m o nit ori n g d e vic e an d r e q uir e d d oc u m e nt ati o n b ac k t o t h e c G M P F acilit y 
 
C h ar act eriz ati o n a n d p hysic al pr o p erti es 
 
T h e n ec ess ar y n u m b er of vi als ar e r e m o v e d f or Fi n al Pr o d uct t esti n g w hic h i ncl u d es c ell d os e/ vi al ( 2 0x 1 0 6 c ells / 1 ml ) or 
1 1 0x 1 0 6 c ells/ 1 0- 1 5 ml/cr y o b a g a n d c ell vi a bilit y b y Tr y p a n Bl u e Excl usi o n ( > 8 0 %), c ell p urit y b y Fl o w C yt o m etric a n al ysis 
( > 9 0 % C D 9 0/ C D 1 0 5; C D 3 4 +/ C D 4 5 + < 5 %), E n d ot oxi n b y E n d ot oxi n P T S ® ( < 1. 6 5 E U/ ml), M yc o pl as m a b y P C R ( n e g ati v e, 
c ells r e-s us p e n d e d i n s p e nt m e di a is c oll ect e d d uri n g t h e l ast ( P 3) h ar v est), a n d 1 4- d a y st erilit y ( acc or di n g t o U S P 
< 7 1 >). U C- M S C Fi n al Pr o d uct is r el e as e d f or a d mi nistr ati o n/t r a ns pl a nt ( Tx) o nl y w h e n all pr o d uct r el e as e crit eri a ar e 
m et.   
T h e d os a g e c h os e n f or a d mi nistr ati o n i n t h e c urr e nt tri al is b as e d o n pr e vi o us ex p eri e nc es of o ur gr o u p a n d ot h ers, 
utilizi n g U C- M S C i ntr a v e n o us t h er a p y.  
 
Pr e p ar ati o n f or A d mi nistr ati o n of U C- M S C:   
W h e n t h e R e q u est f or Tx fr o m st u d y PI/ C o-I is r ec ei v e d , s uffici e nt n u m b er of cr y o vi als/cr y o b a gs c o nt ai ni n g 2 0x 1 06 c ells / 
ml  or  1 1 0x 1 0 6 c ells/ 1 0- 1 5  ml/cr y o b a g  U C- M S C  Fi n al  Pr o d uct  t o  s atisf y  t h e  r e q uir e d  d os e  will  b e  r e m o v e d  fr o m  
L N 2 st or a g e, q uic kl y t h a w e d, sl o wl y dil ut ed i n 4 0- 5 0 ml of Pl as m a-L yt e ( U S P) s u p pl e m e nt e d wit h 1 0 % H S A ( U S P) a n d 
u nfr acti o n at e d H e p ari n ( U S P) 7 0 u nits/ K g of r eci pi e nt b o d y w e i g ht, a n d tr a nsf err e d t o 3 0 0 ml tr a nsf er b a g ( F e n w al, L a k e 
Z uric h, IL) i n pr e p ar ati o n f or i nf usi o n. T h e fi n al c ell s us p e nsi o n  of U C- M S C T h a w e d / Dil ut e d pr o d uct (I P) will b e r el e as e d 
f or  a d mi nistr ati o n  b as e d  o n  ass ess m e nt  of  c ell  d os e  a n d  c ell  vi a bilit y,  Gr a m  st ai n,  E n d ot oxi n,  FL O W  C yt o m etric  
ass ess m e nt of c ell s urf ac e m ar k ers a n d 1 4- d a y st erilit y i m m e di at el y pri or t o tr a nsf er t o t h e fi n al c o nt ai n er ( 3 0 0 ml 
tr a nsf er b a g). F o urt e e n- d a y st erilit y r es ults will s er v e as p ost- pr o d uct r el e as e crit eri a. T h e pr o d uct will b e pl ac e d i n a 
v ali d at e d  tr a ns p ort  c o nt ai n er  fitt e d  wit h  t h e  c o nti n u o us  t e m p er at ur e  m o nit ori n g  d e vic e.  D et ail e d  S O Ps  h a v e  b e e n  
i m pl e m e nt e d f or pr o d uct pr e p ar ati o n f or a d mi nistr ati o n a n d tr a ns p ort t o t h e cli nic al cit e (I nt e nsi v e c ar e u nit, I C U). At 
t h e  ti m e  of  st u d y  i niti ati o n,  I C U  st aff  will  b e  tr ai n e d  o n  h o w  t o  r ec ei v e  t h e  pr o d uct  at  t h e  cli nic al  sit e,  r ec or ds  
r e q uir e m e nts a n d r et ur n of t h e tr a ns p ort c o nt ai n er, t e m p erat ur e m o nit ori n g d e vic e a n d r e q uir e d d oc u m e nt ati o n b ac k 
t o t h e c G M P F acilit y.   
 

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U C- M S C D os e J ustific ati o n a n d C ell I nf usi o n:    
U C- M S C t h er a p y will b e a d mi nist er e d t wic e at a d os e of 1 0 0 x 1 0 6 c ells, wit h t h e s ec o n d i nf usi o n aft er 7 2 +/- 6 h. T h e 
pr o p os e d d os e is b as e d o n pr e vi o us r e p orts wit h cli nic al pr ot oc ols i n v ol vi n g s yst e mic (i. e., I V) a d mi nistr ati o n of U C- M S C 
pr o d ucts, i ncl u di n g A R D S. T h e i nf usi o n, 4 0- 5 0 ml of eit h er ( 1) Pl as m a-L yt e ( U S P) s u p pl e m e nt e d wit h 1 0 % H S A a n d 
u nfr acti o n at e d H e p ari n ( U S P) at a d os e of 7 0 u nits/ K g of r eci pi e nt b o d y w ei g ht  a n d c o nt ai ni n g a d os e of 1 0 0 ± 2 0 x 1 06 of 
I P (i n tr e at m e nt gr o u p), or ( 2) 4 0- 5 0 ml of Pl as m a-L yt e ( US P) s u p pl e m e nt e d wit h 1 0 % H S A a n d u nfr acti o n at e d H e p ari n 
( U S P)  at  a  d os e  of  7 0  u nits/ K g  of  r eci pi e nt  b o d y  w ei g ht  wit h o ut  c ells  (i n  c o ntr ol  gr o u p),  will  b e  a d mi nist er e d  
i ntr a v e n o usl y pr ef er a bl y vi a a c e ntr al li n e. H o w e v er, I P m a y als o b e i nf us e d t hr o u g h a p eri p h er al v e n o us c at h et er if 
c e ntr al li n e is n ot a v ail a bl e. R eci pi e nts a n d c o ntr ols will r e c ei v e pr e m e dic ati o n wit h h y dr oc ortis o n e 5 0 m g I V p us h a n d 
di p h e n h y dr a mi n e 2 5 m g I V p us h 3 0- 6 0 mi n ut es b ef or e a d mi nistr ati o n of I P. At t h e ti m e of pr e m e dic ati o n, if t h e p ati e nt 
is r ec ei vi n g a n i ntr a v e n o us i nf usi o n of H e p ari n, t h e H e p arin i nf usi o n will b e s us p e n d e d f or 2 h o urs i n or d er t o acc o u nt 
f or t h e H e p ari n c o nt ai n e d wit hi n t h e I P. 
  
T h e I P will t h e n b e i nf us e d o v er a p eri o d of 1 0 ± 5 mi n ut es, wit hi n 2 4 h o urs f oll o wi n g st u d y e nr oll m e nt. P ar a m et ers will 
b e a n al yz e d at 7 2 ± 6 h o urs p ost-i nf usi o n. T h e s ec o n d d os e of eit h er ( 1) 1 0 0 ± 2 0 x 1 0 6  I P i n 4 0- 5 0 ml of Pl as m a-L yt e 
s u p pl e m e nt e d wit h 1 0 % H S A ( U S P) a n d u nfr acti o n at e d H e p ari n ( U S P), as a b o v e (i n tr e at m e nt gr o u p), or ( 2) 4 0- 5 0 ml of 
Pl as m a-L yt e s u p pl e m e nt e d wit h 1 0 % H S A ( U S P) a n d u nfr acti o n at e d H e p ari n ( U S P) wit h o ut c ells (i n c o ntr ol gr o u p), will 
b e a d mi nist er e d at 7 2 ± 6 h o urs f oll o wi n g t h e a d mi nistr ati o n of t h e first d os e, wit h pr e m e dic ati o n tr e at m e nt as o utli n e d 
a b o v e.  
 
T h e pr o p os e d d os e is b as e d o n t h e d at a r e p ort e d i n t w o r ec e nt st u di es b y Li a n g et al ( 3 9) a n d L e n g et al ( 3 8) w h o utiliz e d 
a d os e of 1 x 1 0 6 c ells / k g r eci pi e nt b o d y w ei g ht, a d mi nist er e d I V. N o A Es or S A Es w er e r e p ort e d b y t h e a ut h ors i n a n y of 
t h e s u bj ects tr e at e d. B ot h st u di es d e m o nstr at e d t h at M S C tr e at m e nt w as t ol er at e d w ell a n d r es ult e d i n i m pr o v e m e nt i n 
cli nic al o utc o m es, r es ol uti o n of critic al s y m pt o ms, a n d c ess a ti o n i n h os pit al st a y. I n e arli er st u di es i n dic at e d si mil ar 
r es ults. Z h e n g et al( 5 9), i n o n e of t h e first r a n d o miz e d cli nic al tri als p u blis h e d i n A R D S p ati e nts, s h o w e d t h at t h e i nf usi o n 
of a di p os e tiss u e ( A D)- d eri v e d M S Cs ( 1 x 1 0 6 c ells / k g of r eci pi e nt b o d y w ei g ht ( B W) i n 1 0 0 ml n or m al s ali n e w as w ell 
t ol er at e d. I n t his st u d y o n e p ati e nt fr o m e ac h gr o u p, ex p erim e nt al a n d c o ntr ol, d e v el o p e d di arr h e a t h at r es ol v e d wit hi n 
4 8 h o urs. O n e p ati e nt i n M S C gr o u p pr es e nt e d wit h r as h wit h s p o nt a n e o us r es ol uti o n. O n e p ati e nt i n t h e M S C gr o u p 
di e d of m ulti or g a n f ail ur e w hil e t h e s a m e w as o bs er v e d i n 2 p a ti e nts i n c o ntr ol gr o u p. T h e d e at hs w er e c o nsi d er e d t o b e 
r el at e d t o t h e pr e existi n g dis e as e pr oc ess es a n d n ot t o t h e M S C utiliz e d i n t h e st u d y. M att h a y et  al ( 5 1), i n a pr os p ecti v e, 
d o u bl e- bli n d,  m ultic e nt er,  r a n d o miz e d  P h as e  2 a  cli nic al  tri a l, e v al u at e d s af et y of t h e i nf usi o n  of B o n e  M arr o w  ( B M)-
d eri v e d M S Cs (I V, 1 0  x 1 0 6 c ells/ k g) i n 4 3 p ati e nts wit h m o d er at e t o s e v er e A R D S. T h e a ut h ors d e m o nstr at e d t h at e v e n 
w h e n us e d a m uc h hi g h er d os e, t h e tr e at m e nt w as w ell t ol e r at e d wit h 1 d e at h r e p ort e d i n t h e ex p eri m e nt al gr o u p, 
d et er mi n e d t o b e u nr el at e d t o t h e B M- M S C i nf usi o n.  
 
B as e d o n t h e r es ults of pr e vi o us st u di es, w e h y p ot h esiz e t h at t h e us e of t h e U C- M S C c ell ul ar t h er a p y d eli v er e d I V, i n 
C O VI D- 1 9 s u bj ects wit h ALI/ A R D S at st u d y e ntr y will r es ult i n p ositi v e eff ect of  t h e i n v esti g ati o n al t h er a p y i n t er ms of 
r es ol uti o n of cli nic al s y m pt o ms, a n d will d e m o nstr at e t h at U C- M S C t h er a p y at a d os e of 1 0 0 x 1 06  /  i nf usi o n is s af e. 
Alt h o u g h i m m u n os u p pr essi v e pr o p erti es of M S C p os e a p ot e nti a l ris k of n e o pl asi a a n d i nf ecti o n, n o n e of t h es e eff ects 
h a v e b e e n r e p ort e d i n s u bj ects r ec ei vi n g M C Ss t o d at e. N o ot h er s eri o us a d v ers e eff ects ass oci at e d wit h M S C i nf usi o n 
h a v e b e e n r e p ort e d t o d at e. B as e d o n t his i nf or m ati o n, w e b eli v e t h at a d o u bl e d os e of 1 0 0 x 1 0 6 c ells / i nf usi o n is s af e 
a n d mi g ht b e pr o v e n s af e a n d effic aci o us.  
 
T h e i nf usi o n will t a k e pl ac e at I C Us of t h e h os pit als ( e. g. U H e a lt h or J ac ks o n I C U, l oc at e d wit hi n a 5- mi n ut e w al k fr o m t h e 
c G M P F acilit y). T h e ot h er a d diti o n al 5 c e nt ers will b e s u p pli e d i n v esti g ati o n al pr o d uct b as e d o n e nr oll m e nt. U C- M S C 

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i n v esti g ati o n al t h er a p y will b e i nf us e d I V t o m axi miz e t h e pr es e nc e of U C- M S Cs w h er e t h e t h er a p e utic eff ect is m ost 
d esir e d, i. e. i n t h e l u n g. T h e pr oc e d ur e will b e p erf or m e d b y  g ai ni n g v e n o us acc ess t o a p eri p h er al v ei n. O nc e a st a n d ar d 
siz e c at h et er is i n pl ac e, 4 0- 5 0 ml of U C- M S C c o nt ai ni n g 1 0 0 x 1 0
6 c ells/ dil ut e d i n st eril e  Pl as m a-L yt e will b e i nf us e d 
sl o wl y, o v er a p eri o d of 1 0 + 5 mi n. T o pr e v e nt p ost-i nf usi o n c o m plic ati o ns, all s u bj ects will b e m o nit or e d f or 6 h o urs 
p ost-i nf usi o n. A Es a n d S A Es will b e a ss ess e d f or 9 0 d a ys f oll o wi n g tr e at m e nt. 
 
F aciliti es a n d R es o urc es: 
c G M P A dv a nc e d C ell a n d Bi ol o gic Pr o d ucts M a n uf act uri n g F acility :  Est a blis h e d  i n 1 9 9 4 t o d e v el o p n o v el a d v a nc e d 
c ell ul ar t h er a pi es a n d r e g e n er ati v e m e dici n e pr o d ucts c o m p li a nt wit h F e d er al a n d ot h er a p plic a bl e r e g ul ati o ns, f or 
r es e arc h a n d cli nic al a p plic ati o ns. Si nc e its i ns p ecti o n, t h e F acilit y h as s er v e d as a t ec h nic al a n d r e g ul at or y r es o urc e f or 
tr a nsl ati o n al a p plic ati o ns t h at i ncl u d e pr o d uct d e v el o p m e nt, pr oc ess sc al e- u p a n d o pti miz ati o n o p er ati o ns t o e ns ur e 
m axi m u m t hr o u g h p ut. T h e f acilit y m a n uf act ur es, st or es a n d distri b ut es h u m a n c ells, tiss u e a n d c ell ul ar pr o d ucts f or 
cli nic al a p plic ati o ns a n d r es e arc h. T h e f acilit y a n d m a n uf act u r e d pr o d ucts m e et ri g or o us sta n d ar ds p ut f ort h b y t h e F D A 
t o e ns ur e pr o d uct s af et y, i d e ntit y, p urit y, p ot e nc y a n d eff ecti v e n ess. T h e f acilit y is r e gist er e d wit h t h e F D A, a n d is 
accr e dit e d b y F A C T ( F o u n d ati o n f or Accr e dit ati o n of C ell ul ar T h er a pi es) a n d A A B B, a n d is t h e NI H C ell Distri b uti o n C e nt er 
w hic h s er v es i n v esti g at ors at  U M, i n t h e U S, E ur o p e a n d t h e Mi d dl e E ast. T h e F acilit y occ u pi es 1 1, 0 0 0 s q u ar e f e et of 
s p ac e a n d is d e dic at e d t o pr oc essi n g v ari o us t y p es of h u m a n tiss u e a n d c ells. It is l oc at e d o n t h e f o urt h fl o or of t h e 
Di a b et es R es e arc h I nstit ut e, U ni v ersit y of Mi a mi Mill er Sc h o ol of M e dici n e C a m p us. T hr e e cl e a n r o o m s uit es, c ertifi e d t o 
m e et I S O- Cl ass 7 st a n d ar ds, ar e utiliz e d f or c ell a n d d e vic e m a n uf act ur e. T hr e e a d diti o n al l a b or at ori es pr o vi d e a m pl e 
s p ac e f or R & D acti viti es. T h e F acilit y i ncl u d es a R e g ul at or y U nit, t hr e e a d diti o n al l a b or at ori es d e dic at e d t o R & D a n d 
tr a nsl ati o n al w or k, a d e dic at e d cl e a ni n g a n d st eriliz ati o n f acilit y, a n d a r a w m at e ri al r ec ei pt, q u alific ati o n a n d st or a g e 
s p ac e.  
St u dy St atistics 
a.  Pri m ar y o utc o m e v ari a bl e. 
b.  S ec o n d ar y o utc o m e v ari a bl es. 
c. S af et y a n al ysis a n d effic ac y esti m ati o n 
 
Pri m ary o utc o m e v ari a bl es  t o est a blis h s af et y, as d efi n e d b y t h e occ urr e nc e of Pr e-s p ecifi e d I nf usi o n Ass oci at e d 
A d v ers e e v e nts aft er i nf usi o n. A n y of t h e f oll o wi n g occ urri n g wit hi n 6 h p ost e ac h i nf usi o n: 
1. A n i ncr e as e i n v as o pr ess or d os e gr e at er t h a n or e q u al t o t h e f oll o wi n g: 
o  N or e pi n e p hri n e: 1 0 μ g p er mi n  
o  P h e n yl e p hri n e: 1 0 0 μ g p er mi n  
o  D o p a mi n e: 1 0 μ g/ k g p er mi n  
o  E pi n e p hri n e: 1 0 μ g p er mi n  
2. I n p ati e nts r ec ei vi n g m ec h a nic al v e ntil ati o n: w ors e ni n g h y p ox e mi a, as ass ess e d b y a r e q uir e m e nt f or a n 
i ncr e as e of P E E P b y 5 c m H 2 O o v er b as eli n e, or r e q uir e m e nt t o i ncr e as e Fi O 2 of > 2 0 %. 
3. I n p ati e nts r ec ei vi n g hi g h fl o w ox y g e n t h er a p y:  w ors e ni n g h y p ox e mi a, as i n dic at e d b y r e q uir e m e nt of 
i nt u b ati o n a n d m ec h a nic al v e ntil ati o n. 
4. N e w c ar di ac arr h yt h mi a  r e q uiri n g c ar di o v ersi o n 
5. N e w v e ntric ul ar t ac h yc ar di a, v e nt ric ul ar fi brill ati o n, or as yst ol e 
6. A cli nic al sc e n ari o c o nsist e nt wit h tr a nsf usi o n i nc o m p ati bilit y or tr a nsf usi o n-r el at e d i nf ecti o n 
7. C ar di ac arr est or d e at h wit hi n 2 4 h p ost i nf usi o n 
 
I nci d e nc e of S e v er e A d v ers e E v e nts ( S A Es) [ Ti m e Fr a m e: I n v esti g at ors will c o n d uct d ail y ass ess m e nts f or t h e pr es e nc e of 
a n y a d v ers e e v e nts ( A E) fr o m e nr oll m e nt t hr o u g h h os pit al disc h ar g e, a n d t h e n vi a T el e h e alt h  or cli nic al sit e visits]. 
 

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S ec o n d ary o utc o m e v ari a bl es will b e effic ac y si g n als as q u a ntifi e d b y: 
1. Cli nic al o utc o m es t h at i ncl u d e  
•        S ur vi v al at d a y 2 8  
•        S ur vi v al at d a y 6 0   
•        Ti m e t o h os pit al disc h ar g e  
•        V e ntil at or-fr e e d a ys   
•        Ox y g e n tr e at m e nt-fr e e d a ys  
•        I n p ati e nts r ec ei vi n g Hi g h Fl o w Ox y g e n t h er a p y: R O X i n d ex ( S p O 2/ Fi O 2)  
•       I n v e ntil at e d p ati e nts: Ox y g e n ati o n I n d ex ( OI), est a blis h e d b y t h e f oll o wi n g f or m ul a, OI = ( Fi O 2 x 
M P A W)/ P a O 2; w h er e ( Fi O 2 = fr acti o n of i ns pir e d O 2 ; M P A W = M e a n air w a y pr ess ur e ( v e ntil at or); a n d 
P a O 2 = p arti al pr ess ur e of ox y g e n i n art eri al bl o o d)  
•        Dri vi n g Pr ess ur e ( P pl at – P E E P) if a p plic a bl e a n d a v ail a bl e i n t h e el ectr o nic m e dic al r ec or d c h arts  
•        S O F A ( S e q u e nti al Or g a n F ail ur e Ass ess m e nt)   
•        S m ell I d e ntific ati o n T est ( S I T) or olf act or y t esti n g   
  
2. L a b or at or y t esti n g:   
•        C o m pl et e Bl o o d C o u nt ( C B C) wit h diff er e nti al  
•       C o m pre h e nsi ve  M et a b olic P a n el ( M P)  
•        C-r e acti v e pr ot ei n  
•        A A/ E P A r ati o   
o  
•        D- di m er 2 5- O H Vit a mi n D l e v els     
o  All o a nti b o di es ( P a n el R e ac ti v e A nti b o di es [ P R A]) 
o  Vir al L o a d b y S A R S- C o V- 2 R T- P C R   
o  S er ol o g y t esti n g f or S A R S- C o V- 2 I g G/I g M 
  
3. M ec h a nistic st u di es m a y i ncl u d e: 
•  
M ulti pl ex  ELI S A  ass essi n g of pl as m a I nfl a m m at or y p a n el ( # 4 0) of c yt o ki n es, c h e m o ki n es a n d 
gr o wt h f act ors     
•  
ELI S A ass ess m e nt of pl as m a l e v els of S 1 P a n d s P D-L 1   
•  
P B M C ass ess m e nt of T c ell p o p ul ati o ns a, i ncl u di n g:  
o    O v er acti v at e d c yt o ki n e-s ecr eti n g C X C R 3 + C D 4 + T c ells  
o    C X C R 3 + C D 8 + T c ells  
o    C X C R 3 + N K c ells   
o    C D 1 4 + C D 1 1c + C D 1 1 b mi d r e g ul at or y D C c ell p o p ul ati o n  
o    C D 4 + C D 2 5 + F O X P 3 + Tr e gs 
 
P ati e nt d e m o gr a p hics a n d pr e o p er ati v e cli nic al v ari a bl es will b e ex pr ess e d as p erc e nt a g es or m e a ns as a p pr o pri at e, a n d 
will b e ass ess e d usi n g t h e st u d e nt p air e d t-t est a n al ysis: e n d p o i nts will b e c o m p ar e d fr o m t h e b as eli n e t o t h e ti m e p oi nts 
list e d i n t h e Sc h e d ul e of Ass ess m e nt.  If t h e d at a ar e n ot n or m all y distri b ut e d, c o m p ar a bl e n o n- p ar a m etric m et h o ds will 
b e e m pl o y e d. 
   
W e  will  c oll ect  d at a  t o  e v al u at e  ot h er  v ari a bl es  t h at  c a n  als o  i m p act  ox y g e n ati o n,  i ncl u di n g  m o d e  of  m ec h a nic al  
v e ntil ati o n ( e. g. A C/ V C, A C/ P C, A P R V, etc.), P E E P, pl at e a u pr ess ur e, a n d m e a n ai r w a y pr ess ur e. W e will als o d oc u m e nt 
ot h er s u p p orti v e i nt er v e nti o ns pr o vi d e d t o st u d y s u bj ects f or t h e p ur p os e of i m pr o vi n g ox y g e n ati o n, i ncl u di n g pr o n e 
p ositi o ni n g, n e ur o m usc ul ar bl oc k ers ( b ol us or i nf usi o n), as w ell as i n h al e d e p o pr ost e n ol. 
Risks 
 
St u d y M e dic ati o ns: Alt h o u g h U C- M S C c ells h a v e pr e vi o usl y b e e n utiliz e d s af el y, n o g u ar a nt e e c a n b e m a d e of t h e s af et y 
of  t h es e  c ells.  T hr e e  c o nc o mit a nt  m e dic ati o ns  will  b e  gi v e n  al o n g  wit h  t h e  st u d y  m e dic ati o n,  i ncl u di n g  h e p ari n,  

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h y dr oc ortis o n e, a n d di p h e n h y dr a mi n e.  H e p ari n is a n a ntic o a g ul a nt w hic h will b e us e d t o a v oi d p ot e nti al cl otti n g r el at e d 
t o t h e i nf usi o n of c ells.  T h e d os e b ei n g a d mi nist er e d is g e n er all y r e g ar d e d as s af e.  Ris ks of h e p ari n i ncl u d e bl e e di n g or 
all er gic r e acti o ns, w hic h ar e r ar e.  A n y p ati e nt r ec ei vi n g i ntr a v e n o us i nf usi o n of h e p ari n will h a v e t his s us p e n d e d f or 2 
h o urs at t h e ti m e of pr e- m e dic ati o n.  H y dr oc ortis o n e h as b o t h gl uc oc ortic oi d a n d mi n er al oc ortic oi d pr o p erti es. Ris ks of 
si n gl e d os e of h y dr oc ortis o n e s h o ul d b e mi ni m al i n t h e st u d y p o p ul ati o n, b ut m a y i ncl u d e h y p er gl yc e mi a or a n i ncr e as e d 
ris k of i nf ecti o ns.  Di p h e n h y dr a mi n e is a n a nti hist a mi n e, a n d p ossi bl e si d e eff ects i ncl u d e dr o wsi n ess a n d dr y m o ut h.  
T h es e ris ks ar e mi ni m al i n t his st u d y p o p ul ati o n.  
 
I ntr a v e n o us A d mi nistr ati o n of U C- M S C: T h e ris ks ass oci at e d wit h t h e i ntr a- v e n o us a d mi nistr ati o n pr oc e d ur e i ncl u d e 
bl e e di n g, s w elli n g a n d mi n or p ai n o n i nj ecti o n.  T h es e ar e s elf-li miti n g a n d d o n ot p os e a n y l o n g-t er m pr o bl e ms.  T h er e 
is als o a n i nf ecti o us ris k t h at c a n b e tr e at e d wit h a p pro pri at e a nti bi otics. T h e i nf ecti o n m a y c o n d uct c hr o nic p ai n, 
disc o mf ort a n d tiss u e d a m a g e. 
 
Bl o o d t ests: T h e disc o mf ort ass oci at e d wit h r e m o vi n g bl o o d fr o m a v ei n is a sli g ht pi nc h or pi n pric k w h e n t h e st eril e 
n e e dl e e nt ers t h e s ki n. T h e ris ks i ncl u d e mil d disc o mf ort a n d/ or ecc h y m osis at t h e sit e of p u nct ur e. L ess c o m m o n ris ks 
i ncl u d e  a  s m all  bl o o d  cl ot,  i nf ecti o n  or  bl e e di n g  at  t h e  p u nct ur e  sit e,  a n d  o n  r ar e  occ asi o ns  f ai nti n g  d uri n g  t h e  
pr oc e d ur e. 
 
U nf or es e e n ris ks: U nf or es e e n ris ks ar e u nf or es e e n ris ks ar e u n k n o w n ris k s b y r es e arc h ers t h at m a y occ ur as a r es ult of 
t h e st u d y pr oc e d ur es. F or s p ecific i nf or mati o n of t h e p ot e nti al ris ks, pl e as e r ef er att ac h e d i nf or m e d c o ns e nt f or m.  
 
 
St e ps t ak e n t o mi ni miz e t h e risks. 
 
T h e U C- M S C dr u g pr o d uct u n d er g o es ext e nsi v e scr e e ni n g a n d i n- pr oc ess c o ntr ols t o e ns ur e p urit y a n d c o nsist e nc y of 
m a n uf act uri n g.  
 
I ntr a v e n o us a d mi nistr ati o n of st u d y pr o d uct, as w ell as blo o d dr a ws will o nl y b e p erf or m e d b y q u alifi e d, lic e ns e d, 
m e dic al  ex p erts.   Alt h o u g h  u n a ntici p at e d,  t h er e  is  a  h y p o t h etic al  ris k  of  t hr o m b us  f or m ati o n  ass oci at e d  wit h  
a d mi nistr ati o n of a n y c ell ul ar pr o d uct.  S h o ul d t h e p ati e nt ex p eri e nc e s y m pt o ms of t hr o m b osis, b as e d o n t h e p h ysici a n’s 
j u d g m e nt, t h e p ati e nt will b e tr e at e d f or t hr o m b o e m b olis ms as p er I C U pr ot oc ol.  
 
U n a ntici p at e d pr o bl e ms 
 
T h e Offic e f or H u m a n R es e arc h Pr ot ecti o ns ( O H R P) c o nsi d ers u n a ntici p at e d pr o bl e ms i n v ol vi n g ris ks t o p artici p a nts or 
ot h ers t o i ncl u d e, i n g e n er al, a n y i nci d e nt, ex p eri e nc e, or o utc o m e t h at m e ets all of t h e f oll o wi n g crit eri a: 
 
•  
U n ex p ect e d i n t er ms of n at ur e, s e v erit y, or fr e q u e nc y giv e n ( a) t h e r es e arc h pr oc e d ur es t h at ar e d escri b e d i n 
t h e pr ot oc ol-r el at e d d oc u m e nts, s uc h as t h e I nstit uti on al R e vi e w B o ar d (I R B)- a p pr o v e d r es e arc h pr ot oc ol a n d 
i nf or m e d c o ns e nt d oc u m e nt; a n d ( b) t h e c h ar act eristics of t h e p artici p a nt p o p ul ati o n b ei n g st u di e d; 
•  
R el at e d or p ossi bl y r el at e d t o p artici p ati o n i n t h e r es e arc h (“ p ossi bl y r el at e d” m e a ns t h er e is a r e as o n a bl e 
p ossi bilit y t h at t h e i nci d e nt, ex p eri e nc e , or o utc o m e m a y h a v e b e e n c a us e d b y t h e pr oc e d ur es i nv ol v e d i n t h e 
r es e arc h); a n d 
•  
S u g g ests  t h at  t h e  r es e arc h  pl ac es  p artici p a nts  or  ot h ers  at  a  gr e at er  ris k  of  h ar m  (i ncl u di n g  p h ysic al,  
ps yc h ol o gic al, ec o n o mic, or s oci al h ar m) t h a n w as pr e vi o usl y k n o w n or r ec o g niz e d. 
 
Pl a n f or r e p orti n g u n a ntici p at e d pr o bl e ms or st u dy d evi ati o ns. 
 
T h e i n v esti g at or will r e p ort u n a ntici p at e d pr o bl e ms ( U Ps) t o t h e r e vi e wi n g I nstit uti o n al R e vi e w B o ar d (I R B) a n d l e a d 
pri nci p al i n v esti g at or ( PI/s p o ns or of t h e tri al). T h e U P r e p ort will i ncl u d e t h e f oll o wi n g i nf or m ati o n: 

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- Pr ot oc ol i d e ntif yi n g i nf or m ati o n: pr ot oc ol titl e a n d n u m b er, PI’s n a m e, a n d t h e I R B pr oj ect n u m b er; 
- A d et ail e d d escri pti o n of t h e e v e nt, i nci d e nt, ex p eri e nc e, or o utc o m e;  
- A n ex pl a n ati o n of t h e b asis f or d et er mi ni n g t h at t h e e v e n t, i nci d e nt, ex p eri e nc e, or o utc o m e r e pr es e nts a n U P;  
- A d escri pti o n of a n y c h a n g es t o t h e pr ot oc ol or ot h er c orr ecti v e ac ti o ns t h at h a v e b e e n t a k e n or ar e pr o p os e d i n 
r es p o ns e t o t h e U P. 
 
T o s atisf y t h e r e q uir e m e nt f or pr o m pt r e p orti n g, U P s will b e r e p ort e d usi n g t h e f oll o wi n g ti m eli n e:   
 
- U Ps t h at ar e s eri o us a d v ers e e v e nts ( S A E s) will b e r e p ort e d t o t h e I R B a n d t o t h e st u d y s p o ns or wit hi n 2 4 hrs. of 
t h e i n v esti g at or b ec o mi n g a w ar e of t h e e v e nt.  
- A n y ot h er U P will b e r e p ort e d t o t h e I R B a n d t o t h e 7 d a ys  of t h e i n v esti g at or b ec o mi n g a w ar e of t h e pr o bl e m.  
- All U Ps s h o ul d b e r e p ort e d t o a p pr o pri at e i nstit uti o n al o ffici als ( as r e q uir e d b y a n i nstit uti o n’s writt e n r e p orti n g 
pr oc e d ur es),  t h e  s u p p orti n g  a g e nc y  h e a d  ( or  d esi g n e e),  a n d  t h e  Offic e  f or  H u m a n  R es e arc h  Pr ot ecti o ns  
( O H R P) wit hi n 3 0 d a ys of t h e I R B’s r ec ei pt of t he r e p ort of t h e pr o bl e m fr o m t h e i n v esti g at or. 
 
Mi n or st u d y d e vi ati o ns ar e p er mitt e d w h e n a p pr o v e d b y t h e s p o ns or a n d i n v esti g at or.   
 
A list of p ossi bl e d e vi ati o ns a n d m e a ns of a d dr essi n g is pr o vi d e d b el o w: 
 
Scr e e n F ail ur es : A scr e e n f ail ur e s u bj ect is o n e fr o m w h o i nf or m e d c o ns e nt is o bt ai n e d, b ut tr e at m e nt wit h t h e 
i n v esti g ati o n al t h er a p y w as n ot att e m pt e d b ec a us e it w as d et er mi n e d ( aft er t h e s u bj ect si g n e d t h e i nf or m e d c o ns e nt 
f or m) t h at t h e s u bj ect di d n ot m e et all of t h e eli gi bilit y crit eri a. T h e n u m b er of scr e e n f ail ur e s u bj ects will b e r e p ort e d, 
b ut s uc h s u bj ects will n ot b e i ncl u d e d eit h er i n t h e i nt e nt-t o-tr e at or t h e p er pr ot oc ol a n al ysis.   
 
Wit h dr a w al Crit eri a a n d Pr oc e d ur es : All s u bj ects h a v e t h e ri g ht t o wit h dr a w wit h o ut pr ej u dic e at a n y p oi nt d uri n g 
tr e at m e nt.  T h e i n v esti g at or c a n wit h dr a w a n y s u bj ect fr o m i n v esti g ati o n al tr e at m e nt at a n y ti m e if d e e m e d m e dic all y 
n ec ess ar y.  S uc h s u bj ects will r e m ai n i n t h e st u d y f or p ur p os es of a n al ysis, f or b ot h s af et y a n d acti vit y, as a p pr o pri at e. 
T h e r e as o n f or t h e s u bj ect’s wit h dr a w al s h o ul d b e d oc u m e nt e d o n t h e a p pr o pri at e c as e  r e p ort f or m.  Wit h dr a w n 
s u bj ects will n ot b e r e pl ac e d. T h e s p o ns or s h o ul d b e n otifi e d  pr o m ptl y w h e n a s u bj ect is wit h dr a w n, pr ef er a bl y wit hi n 
4 8 h o urs.  
 
Miss e d Cli nic Visits : A n y s u bj ect w h o d o es n ot r et ur n f or a sc h e d ul e d f oll o w- u p visit will b e c o nt act e d at l e ast t wic e b y 
t el e p h o n e t o d et er mi n e t h e c a us e f or t h e miss e d visit. All att e m pts t o c o nt act t h es e s u bj ects will b e r ec or d e d i n t h e 
s u bj ect’s r ec or ds.  If t h e s u bj ect is c o nt act e d, a n e w visit w ill b e sc h e d ul e d as s o o n as p ossi bl e.  S uc h s u bj ects will b e 
c o nsi d er e d as m aj or pr ot oc ol vi ol at ors a n d m a y b e excl u d e d fr o m t h e p er pr ot oc ol a n al ysis.  T h e y will h o w e v er b e 
i ncl u d e d i n t h e i nt e nt-t o-tr e at (I T T) a n alysis acc or di n g t h eir act u al d at a. S u bj ects  will als o b e excl u d e d fr o m t h e p er 
pr ot oc ol a n al ysis if t h e y miss m or e t h a n 1/ 3 of t h eir sc h e d ul e d visits.  A n exc e pti o n will b e m a d e f or visits miss e d as a 
r es ult of h os pit aliz ati o n.  I n a d diti o n, p ati e nts m a y b e exclu d e d fr o m a p er pr ot oc ol a n al ys is if t h e y ar e r e p e at e dl y n o n-
c o m pli a nt wit h m e dic al g ui d a nc e (i. e., a nti bi otics, w o u n d c ar e , c h ol est er ol m e ds, etc.) d es pit e r e p e at e d cl arific ati o n a n d 
r ei nf orc e m e nt fr o m t h e p h ysici a n a n d s u p p ort st aff.  I n all c as es t h e s u bj ects r ec ei vi n g t h e U C- M S C pr o d uct will b e 
a n al yz e d i n t h e i nt e nti o n t o tr e at a n al ysis, w hic h is t h e pri m ar y o utc o m e m e as ur e i n t his st u d y. 
 
Pr ot oc ol D evi ati o ns : Exc e pt f or e m er g e nc y sit u ati o ns, t his st u d y s h o ul d  b e c o n d uct e d as d escri b e d i n t his pr ot oc ol. A n 
ex a m pl e of s uc h a n e m er g e nc y sit u ati o n is o n e i n w hic h t h e pr ot ecti o n, s af et y a n d w ell- b ei n g of a s u bj ect r e q uir es a 
pr ot oc ol d e vi ati o n; t his d e vi ati o n w o ul d b e b as e d u p o n t h e j u d g m e nt of t h e i n v esti g at or  ( or a r es p o nsi bl e p h ysici a n, 
a p pr o pri at el y tr ai n e d d esi g n at e d b y t h e i n v esti g at or). If a d e vi ati o n fr o m t h e pr ot oc ol is n e c ess ar y t o pr ot ect t h e lif e a n d 
p h ysic al w ell- b ei n g of a s u bj ect i n a n e m er g e nc y, s uc h pr ot oc ol d e vi ati o ns m ust b e r e p ort e d t o t h e s p o ns or a n d t h e 
r e vi e wi n g I R B or I E C as s o o n as p ossi bl e, b ut n o l at er t h a n fi v e w or ki n g d a ys aft er t h e e m er g e nc y occ urr e d.  I n t h e e v e nt 
of a si g nific a nt d e vi ati o n fr o m t h e pr ot oc ol d u e t o a n acci d e nt  or mist a k e, t h e i n v esti g at or or d esi g n e e m ust c o nt act t h e 
s p o ns or at t h e e arli est p ossi bl e ti m e b y t el e p h o n e t o di sc uss t h e d e vi ati o n a n d its i m p act o n t h e st u d y, a n d t h at 

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s u bj ect’s  c o nti n u e d  p artici p ati o n  i n  t he  st u d y.  T h es e  disc ussi o ns  will  b e  d oc u m e nt e d  b y  t h e  i n v esti g at or  a n d  t h e  
s p o ns or, a n d r e vi e w e d b y t h e m o nit or.  
 
Pr e m at ur e E n d of St u dy : All  s u bj ects  w h o  h a v e  si g n e d  a n  i nf or m e d  c o ns e nt,  exc e pt  f or  scr e e n  f ail ur es,  will  b e  
c o nsi d er e d t o h a v e e nr oll e d i n t h e st u d y. S u bj ects w h o c o m pl et e 2 8- d a y st u d y d ur ati o n will b e c o nsi d er e d t o h a v e 
c o m pl et e d t h e st u d y. All s u bj ects s h o ul d h o w e v er b e f oll o w e d u ntil c o m pl eti n g t h e st u d y f oll o w- u p 9 0 d a ys aft er 
tr e at m e nt or u ntil st u d y disc o nti n u ati o n f or ot h er r e as o ns. T h e r e as o n f or st u d y disc o nti n u ati o n s h o ul d b e d oc u m e nt e d 
f or e ac h s u bj ect.  
 
M e dic ati o n C h a n g es :  M e dic ati o ns list e d i n t h e excl usi o n s el ecti o n crit eri a ar e pr o hi bit e d fr o m t his st u d y pri or t o 
e nr oll m e nt o nl y. If t h e s u bj ect r ec ei v es a n y m e dic ati o n t h at is  list e d i n t h e excl usi o n ar y criteri a aft er tr e at m e nt, h e/s h e 
will n ot b e wit h dr a w n fr o m t h e st u d y.  
 
U n bli n di n g : T h e pr ot oc ol i n v ol v es bli n d e d tr e at m e nt all oc ati o n f or b ot h t h e cli nici a ns dir ectl y i n v ol v e d i n t h e c ar e of t h e 
p ati e nt a n d t h e st u d y t e a m ass essi n g t h e p a ti e nt, a n d will b e f acilit at e d b y pr o vi di n g t o t h e c o ntr ol gr o u p i nf usi o ns of 
Pl as m a-L yt e wit h e q u al d os es of H S A a n d h e p ari n as t h e tr e at m e nt gr o u p, as w ell as a n i d e ntic al pr e- m e dic ati o n 
r e gi m e n.  If u n bli n di n g of eit h er t h e cli nic al t e a m or i n v esti g at or w er e t o occ ur i n a d v ert e ntl y, t his d e vi ati o n w o ul d b e 
r ec or d e d, a n d a n ot h er i n v esti g at or w o uld b e assi g n e d t o ass ess f or st u d y-r el at e d o utc o m es.  T h e cli nic al t e a m m a y 
r e q u est u n bli n di n g f or r e as o ns of p ati e nt s af et y, a n d t his c a n occ ur wit h t h e a p pr o v al of t h e PI, if it is d e e m e d n ec ess ar y 
f or t h e s af et y of t h e p ati e nt (f or ex a m pl e a s us p ect e d a n a p h yl actic r e acti o n).   
 
B e n efits 
 
T h e us e of U C- M S C f or A R D S ass oci at e d wit h C O VI D- 1 9 is ex p e ri m e nt al, a n d m a y n ot r es ult i n a n y dir ect b e n efit t o t h e 
p ati e nt.  P artici p ati o n i n t his st u d y m a y h el p t h e p ati e nt f e el b ett er or h a v e a n o bj ecti v e i m pr o v e m e nt, alt h o u g h n o 
g u ar a nt e e c a n b e m a d e. T h e i nf or m ati o n o bt ai n e d i n t his tri a l m a y pr o v e t o b e us ef ul t o ot h ers wit h C O VI D- 1 9 a n d m a y 
als o c o ntri b ut e t o a b ett er u n d erst a n di n g of t h e c o n diti o n a n d p ot e nti al of c ell t h er a p y f or tr e at m e nt of C O VI D- 1 9.  
K n o wl e d g e g ai n e d fr o m t his st u d y m a y h el p i n d e v el o pi n g n e w tr e at m e nts f or ot h er i n di vi d u als.   
 
A dv ers e Ev e nts  
 
Ev al u ati o n of A dv ers e Ev e nts: 
 
A d v ers e e v e nt m e a ns a n y u nt o w ar d m e dic al occ urr e nc e ass oci at e d wit h t h e us e of a n i nt er v e nti o n i n h u m a ns, w h et h er 
or n ot c o nsi d er e d i n t er v e nti o n-r el at e d ( 2 1 C F R 3 1 2. 3 2 ( a)). 
 
A d v ers e e v e nts occ urri n g d uri n g t h e c o urs e of t h e cli nic al st u d y  s h o ul d b e r e p ort e d t o t h e s p o ns or a n d t h e l oc al I R B, a n d 
d oc u m e nt e d o n t h e A d v ers e E v e nt c as e r e p ort f or ms. T his r e p orti n g will i ncl u d e a n ass ess m e nt of t h e a d v ers e e v e nt, its 
tr e at m e nt a n d r es ol uti o n, a n d its r el ati o ns hi p t o t h e U C- M S C tr e at m e nt.  T h e s po ns or will r e vi e w all r e p orts of a d v ers e 
e v e nts wit h t h eir m e dic al a d vis or.  
 
 
D efi niti o ns ( a dv ers e ev e nts):  
 
A n a d v ers e e v e nt ( A E) is d efi n e d as a n y n e w m e dic al pr o bl e m, or ex ac er b ati o n of a n existi n g pr o bl e m, ex p eri e nc e d b y a 
s u bj ect w hil e e nr oll e d i n t h e st u d y, w h et h er or n ot it is c o nsi d er e d t h er a p y-r el at e d b y t h e i n v esti g at or.  
 

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R el ati o ns hi p of A dv ers e Ev e nts ( A Es) t o t h e U C- MS C I nv esti g ati o n al Pr o d uct (I P):  
 
T h e i n v esti g at or s h o ul d ass ess t h e r el ati o ns hi p of t h e A E t o t h e I P.  T h e r el a ti o ns hi p s h o ul d b e ass ess e d usi n g t h e 
f oll o wi n g c at e g ori es:   
 
•  
D efi nit e: A dir ect c a us e a n d eff ect r el ati o ns hi p b e t w e e n t h e U C- M S C a n d t h e a d v ers e e v e nt exists.   
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Pr o b a bl e: A dir ect c a us e a n d eff ect r el ati o ns hi p b e t w e e n t h e U C- M S C a n d t h e a d v ers e e v e nt h as n ot b e e n 
cl e arl y d e m o nstr at e d, b ut is li k el y or v er y li k el y.  
•  
P ossi bl e: A dir ect c a us e a n d eff ect r el ati o ns hi p b et w e e n t h e U C- M S C a n d t h e a d v ers e e v e nt is n ot li k el y, b ut m a y 
exist. 
•  
N ot Li k el y:  A dir ect c a us e a n d eff ect r el ati o ns hi p b et w e e n t h e U C- M S C us e a n d t h e a d v ers e e v e nt h as n ot b e e n 
d e m o nstr at e d or is i m pr o b a bl e, b ut n ot i m p ossi bl e.   
•  
U nr el at e d: T h e a d v ers e e v e nt is d efi nit el y n ot ass oci at e d wit h t h e U C- M S C. 
 
U n a ntici p at e d A dv ers e Eff ects ( Ev e nts) 
 
A n u n a ntici p at e d a d v ers e eff ect is d efi n e d as “ a n y s eri o us a d v ers e eff ect o n h e alt h or s af et y, or a n y lif e-t hr e at e ni n g 
pr o bl e m or s u bj ect d e at h c a us e d if t h at eff ect, is a pr o bl e m t h at w as n ot pr e vi o usl y i d e ntifi e d i n n at ur e, s e v erit y, or 
d e gr e e  of  i nci d e nc e  i n t h e i n v esti g ati o n al pl a n,  or, or a n y  ot h er u n a ntici p at e d  s eri o us pr o bl e m ass oci at e d wit h a  
tr e at m e nt t h at r el at es t o t h e ri g hts, s af et y, or w elf ar e of s u bj ects.” 
 
If a n u n a ntici p at e d a d v ers e eff ect occ urs, t h e i n v esti g at or m ust pr o m ptl y n otif y t h e s p o ns or of s uc h a n e v e nt wit hi n 2 4 
h o urs of first l e ar ni n g of t h e e v e nt. T h e i n v esti g at or m ust pr o m ptl y n otif y t h e I R B of s uc h a n e v e nt as s o o n as p ossi bl e, 
b ut n o l at er t h a n t e n ( 1 0) w or ki n g d a ys aft er first l e ar ni n g of t h e e v e nt. 
 
S eri o us A dv ers e Ev e nts (S A Es) 
 
A n A E or s us p ect e d a d v ers e r e acti o n is c o ns i d er e d "s eri o us" if, i n t h e vi e w of eit h er t h e i n v esti g at or or s p o ns or, it r es ults 
i n a n y of t h e f oll o wi n g o utc o m es:  
1.  R es ults i n, or c o ntri b ut es t o, a d e at h;  
2.  Is lif e-t hr e at e ni n g (i. e., t h e s u bj ect w as, i n t h e o pi ni o n of t h e i n v esti g at or, at ris k of d e at h at t h e ti m e of t h e 
e v e nt b ut it d o es n ot i ncl u d e a n e v e nt t h at, h a d it occ urr e d i n a m or e  s e v er e f or m, mi g ht h a v e c a us e d d e at h); 
3.  R es ults i n p er m a n e nt dis a bilit y or i nc a p acit y (i. e., p e r m a n e nt i m p air m e nt of a b od y f u ncti o n or p er m a n e nt 
d a m a g e t o a b o d y str uct ur e); 
4.  Pr ol o n gs h os pit aliz ati o n; 
5.  N ec essit at es m e dic al or s ur gic al i nt er v e nti o n t o pr ecl u d e a p er m a n e nt dis a bilit y or i nc a p acit y; a n d, 
6.  R es ults i n a c o n g e nit al a n o m al y or birt h d ef ect.   
 
I m p ort a nt m e dic al e v e nts t h at m a y n ot r es ult i n d e at h, b e life-t hr e at e ni n g, or r e q uir e h os pit aliz ati o n m a y b e c o nsi d er e d 
s eri o us w h e n, b as e d u p o n a p pr o pri at e m e dic al j u d g m e nt, t h e y m a y j e o p ar diz e t h e p artici p a nt a n d m a y r e q uir e m e dic al 
or s ur gic al i nt er v e nti o n t o pr e v e nt o n e of t h e o utc o m es lis t e d i n t his d efi niti o n. N o n-s eri o us a d v ers e e v e nts ar e all 
e v e nts t h at d o n ot m e et t h e crit eri a f or a “s eri o us” a d v ers e e v e nt. 
 
 
A d diti o n al R e p orti n g R e q uir e m e nts 
 
T h e s p o ns or will ex p e dit e r e p orti n g t o t h e I R B, a n d F D A ( vi a I N D s af et y r e p orts) t h at ar e at l e ast p ossi bl y r el at e d t o t h e 
st u d y pr oc e d ur es or d u e t o u n ex p ect e d w ors e ni n g of t h e p ati e nt’s u n d erl yi n g dis e as e.  T h e i n v esti g at or will m a k e a n d 
r ec or d t his d et er mi n ati o n o n t h e A E r e p orti n g f or m.  T h es e will b e b as e d o n C E E P C o m m o n T er mi n ol o g y Crit eri a f or 
A d v ers e E v e nts ( C T C A E). A n y s us p ect e d a d v ers e r e acti o n t h at is b ot h s eri o us a n d u n ex p ect e d, i ncl u di n g d e at h, will b e 

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r e p ort e d  t o  F D A  n o  l at er  t h a n  1 5  d a ys  aft er  t h e  s p o ns or  d et er mi n es  t h at  t h e  i nf or mati o n  q u alifi es  f or  r e p orti n g  
A writt e n s u m m ar y of t h e r es ults of t h e tr e at m e nt, i ncl u di n g  a d v ers e e v e nts at t h e e n d of 9 0- d a y f oll o w u p, will b e 
pr o vi d e d t o F D A.  
 
D e at hs 
 
T h e i n v esti g at or m ust n otif y t h e s p o ns or as s o o n as p ossi bl e, pr ef er a bl y wit hi n 2 4 h o urs b ut i n n o e v e nt l at er t h a n 4 8 
h o urs, of l e ar ni n g of a s u bj ect’s d e at h —r e g ar dl ess of w h et h e r t h e d e at h is r el at e d or u nr el at e d t o t h e U C- M S C pr o d uct 
u n d er i n v esti g ati o n al p h as e, t h e i n v esti g at or s h o ul d att e m pt t o d et er mi n e, as c o ncl usi v el y as p ossi bl e, w h et h er t h e 
d e at h is r el at e d t o t h e st u d y.  T h e c a us e of d e at h a n d t h e i n v esti g at or’s disc ussi o n r e g ar di n g w h et h er or n ot t h e d e at h 
w as tr e at m e nt r el at e d s h o ul d b e d escri b e d i n a writt e n r e p ort. 
 
Pr e- existi n g C o n diti o ns 
 
A pr e- existi n g c o n diti o n s h o ul d n ot b e r e p ort e d as a n a d v ers e e v e nt u nl ess t h er e h as b e e n a s u bst a nti al i ncr e as e i n 
s e v erit y or fr e q u e nc y of t h e pr o bl e m t h at h as n ot b e e n attri b ut e d t o n at ur al hist or y. 
 
Cli nic al L a b or at ory C h a n g es  
 
T h e i n v esti g at or s h o ul d r e vi e w t h e r es ults of all l a b or at or y t ests as t h e y b ec o m e a v ail a bl e.  F or e ac h l a b or at or y t est 
r es ult, t h e i n v esti g at or n e e ds t o asc ert ai n if t his is a n a b n or m al (i. e., cli nic all y si g nific a nt) c h a n g e fr o m b as eli n e f or t h at 
i n di vi d u al s u bj ect. ( T his d et er mi n ati o n, h o w e v er, d o es n ot n ec ess aril y n e e d t o b e m a d e t h e first ti m e a n a b n or m al v al u e 
is o bs er v e d. T h e i n v esti g at or m a y r e p e at t h e l a b or at or y t est or r e q u est a d diti o n al t ests t o v erif y t h e r es ults of t h e 
ori gi n al l a b or at or y t ests). If t his l a b or at or y v al u e is d et er mi n e d t o b e a n a b n or m al c h a n g e fr o m b as eli n e f or t h at s u bj ect, 
t his s h o ul d b e c o nsi d er e d a n a d v ers e e v e nt.  
 
P artic ul ar att e nti o n will b e p ai d t o c li nic al o utc o m es a n d l a b or at or y v al u es. 
 
Eliciti n g a n d R e p orti n g A dv ers e Ev e nt  
T h e i nv esti g at or will ass ess s u bj ects f or t h e occ urr e nc e of a d v ers e e v e nts at e ac h st u d y visit.  I n or d er t o a v oi d bi as i n 
eliciti n g a d v ers e e v e nts, s u bj ects s h o ul d b e as k e d t h e f oll o wi n g n o n-l e a di n g q u esti o n: “ H o w h a v e y o u f elt si nc e y o ur l ast 
visit ?”  All a d v ers e e v e nts (s eri o us a n d n o n-s eri o us) r e p ort e d  b y t h e s u bj ect m ust b e r ec or d e d o n t h e s o urc e d oc u m e nts 
a n d c as e r e p ort f or ms pr o v i d e d b y t h e s p o ns or.   
  
R e p orti n g R e q uir e m e nts f or S eri o us A dv ers e Ev e nts  
T h e i n v esti g at or s h o ul d r e p ort a n y s eri o u s a d v ers e e v e nts b y t el e p h o n e t o t h e sit e I R B acc or di n g t o i nstit uti o n p olici es. 
T h e sit e r es e arc h c o or di n at or s h o ul d r e p o rt t his a d v ers e e v e nt t o t h e S p o ns or b y el ectr o nic m e a ns wit hi n 2 4 h o urs aft er 
r ec ei pt of i nf or m ati o n fr o m t h e i n v esti g at or.  S u bj ects ex p eri e nci n g s eri o us a d v ers e e v e nts s h o ul d b e f oll o w e d cli nic all y 
u ntil t h eir h e alt h h as r et ur n e d t o b as eli n e st at us or u ntil a ll p ar a m et ers h a v e r et ur n e d t o n or m al, or h a v e ot h er wis e 
b e e n ex pl ai n e d.  T h e i n v esti g at or m ust als o c o m pl y wit h a n y ot h er r e q uir e m e nts f or r e p orti n g A d v ers e E v e nts, w hic h ar e 
i m p os e d b y t h e I R B.  T h e st u d y’s St atistic al M a n a g er will als o pr o vi d e t h e D at a S af et y M o nit ori n g B o ar d wit h all s eri o us 
a d v ers e e v e nt r e p orts. 
 
T h e st u d y cli nici a n will i m m e di at el y r e p ort a n y s eri o us a d v e rs e e v e nt, w h et h er or n ot c onsi d er e d st u d y i nt er v e nti o n 
r el at e d,  i ncl u di n g  t h os e  list e d  i n  t h e  pr ot oc ol  a n d  m ust  i ncl u d e  a n  ass ess m e nt  of  w het h er  t h er e  is  a  r e as o n a bl e  
p ossi bilit y t h at t h e st u d y i nt er v e nti o n c a us e d t h e e v e nt. St u d y e n d p oi nts t h at ar e s eri o us a d v ers e e v e nts ( e. g., all-c a us e 
m ort alit y) m ust b e r e p ort e d i n acc or d a nc e wit h t h e pr ot ocol u nl ess t h er e is e vi d e nc e s u g g esti n g a c a us al r el ati o ns hi p 
b et w e e n  t h e  st u d y  i nt er v e nti o n  a n d  t h e  e v e nt  ( e. g.,  d e at h  fr o m  a n a p h yl axis).  I n  t h at  c as e,  t h e  i n v esti g at or  m ust  
i m m e di at el y r e p ort t h e e v e nt t o t h e s p o ns or. 
 

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C o nfi de ntial
  
All s eri o us a d v ers e e v e nts ( S A Es) will b e f oll o w e d u ntil s atisf act or y r es ol uti o n or u ntil t h e tr e ati n g st u d y i nv esti g at or 
a n d/ or i n v esti g at or s p o ns or d e e ms t h e e v e nt t o b e c hr o nic or t h e p artici p a nt is st a bl e. Ot h er s u p p orti n g d oc u m e nt ati o n 
of t h e e v e nt will b e pr o vi d e d t o t h e r e vi e w i n g e ntiti es (I R B of r ec or d, D S M B, F D A etc.) a n d s h o ul d b e pr o vi d e d as s o o n as 
p ossi bl e. 
 
T h e st u d y s p o ns or will b e r es p o nsi bl e f or n otif yi n g t h e F o o d a n d Dr u g A d mi nistr ati o n ( F D A) of a n y u n ex p ect e d f at al or 
lif e-t hr e at e ni n g s us p ect e d a d v ers e r e acti o n as s o o n as p ossi bl e, b ut i n n o c as e l at er t h a n 7 c al e n d ar d a ys aft er t h e 
s p o ns or's i niti al r ec ei pt of t h e i nf or m ati o n.  I n a d diti o n, t h e s p o ns or m ust n otif y F D A a n d all p artici p at i n g i n v esti g at ors i n 
a n I n v esti g ati o n al N e w Dr u g (I N D) s af et y r e p ort of p ot e nti al s eri o us ris ks, fr o m cli nic al tri als  or a n y ot h er s o urc e, as s o o n 
as p ossi bl e, b ut i n n o c as e l at er t h a n 1 5 c al e n d ar d a ys af t er t h e s p o ns or d et er mi n es t h at t h e i nf or m ati o n q u alifi es f or 
r e p orti n g. 
 
Ass ess m e nt of S af ety 
 
Pri m ary S af ety E n d p oi nt 
All a d v ers e e v e nts will b e r e p ort e d i n t er ms of s e v erit y, r e l ati o n t o st u d y tr e at m e nt, d urati o n, r es ol uti o n, a n d p ati e nt 
o utc o m e.      
 
T h e st u d y will b e h alt e d if t h e Pri nci p al I n v esti g at or d et er m i n es t h at a si g nific a nt n u m b er of s eri o us a d v ers e e v e nts ar e 
dir ectl y attri b ut a bl e t h e i nf usi o n pr ot oc ol or t h at t h e o v er all r at e of s e v er e a d v ers e e v e nts i n t his st u d y gr o u p is 
si g nific a ntl y gr e at er t h a n t h at pr e dict e d b y t h e n at ur al hist or y of dis e as e i n t his gr o u p or t h a n as o bs er v e d i n t h e c o ntr ol 
gr o u p.  
 
T h e st u d y will h a v e t w o a n al ysis r e p orts. T h e first is t h e i n t eri m a n al ysis p ost-i nf usi o n of 6 p ati e nts i n t h e tr e at m e nt 
gr o u p. T h e p ur p os e of t his r e p ort is t o pr o vi d e a n e arl y pr eli mi n ar y i nt eri m a n al ysis, w hic h w o ul d all o w f or ass ess m e nt 
of t h e  s af et y of i nf usi n g t h e c ell ul ar c o m p ositi o n. T his r e p ort will ex a mi n e d at a t o ass ess ac ut e r es p o ns e t o t h e i nf usi o n 
pr ot oc ol a n d/ or t h e tr e ati n g c o m p ositi o n. D at a t a k e n at b as eli n e, d a y of disc h ar g e, a n d t hr e e m o nt hs will b e a n al yz e d t o 
d et er mi n e a n y i m m e di at e a d v ers e e v e nts r el at e d t o tr e at m e nt.  
 
T h e D at a S af et y M o nit ori n g B o ar d ( D S M B) will r e vi e w t h e i n t eri m a n d r ec o m m e n d eit h er c onti n ui n g t h e tri al or h alti n g 
t h e tri al b as e d o n t h e r at e of a d v ers e e v e nts a n d S A Es. 
 
T h e tri al will b e pl ac e d o n h ol d a n d r e vi e w e d b y t h e D S M B if t h e f oll o wi n g occ ur: 
•  
A n y d e at h wit hi n 1 4 d a ys aft er i nf usi o n t h at is c o nsi d er e d t o b e p ossi bl y r el at e d t o t h e i nf usi o n of st u d y pr o d uct. 
•  
A m ar k e d i ncr e as e i n tr o p o ni n 5x b as eli n e or n e w n e ur ol o gic al e v e nt. 
 
D at a S af ety a n d S u p ervisi o n 
 
T h er e will b e a D at a S af et y M o nit ori n g B o ar d ( D S M B) of 3 p h y sici a ns t o r e vi e w st u d y d at a q u art erl y t o e ns ur e p ati e nt 
s af et y. 
 
T h e c h air of t h e D S M B will b e i nf or m e d of all d e at hs, s eri o us u n ex p ect e d a d v ers e e v e nts, a n d all s eri o us a d v ers e e v e nts 
i m m e di at el y aft er t h e s p o ns or h as b e e n n otifi e d.  T h e c h air of t h e D S M B will r ec ei v e a r e p ort of a n e v e nt as s o o n as t h e 
S p o ns or r ec ei v es t h e r e p ort fr o m t h e i n v esti g at or.  T h e r e p ort will t h e n b e r e vi e w e d b y t h e f ull D S M B.   
 
St o p pi n g R ul es 
 

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W h e n a n i n v esti g at or i d e ntifi es a n e v e nt p ot e nti all y ass oci at e d wit h a st o p pi n g r ul e n ot e d b el o w, t h e i n v esti g at or m ust 
n otif y s p o ns or i m m e di at el y.  S p o ns or will t h e n n otif y t h e D S M B.  T h e D S M B will d et er mi n e if t h e st o p pi n g r ul es s h all b e 
i n v o k e d.   
 
S af et y st o p pi n g r ul es m a y b e i n v o k e d b y t h e D S M B u p o n n otific ati o n of t h e f oll o wi n g: 
 
•  
P ati e nt  d e at h  w h er e  t h e  i nci d e nt  is  p ossi bl y  r el at e d  t o  t h e  tr e at m e nt  (i. e.  C ell  pr o d uct  or  a d mi nistr ati o n  
pr oc e d ur e).  R est art of t h e st u d y will b e gi n u p o n a p pr o v al of t h e D S M B. 
•  
S eri o us a d v ers e r e p orts fr o m a n y of t h e first 3 p ati e nts  p ot e nti all y i n r el ati o n t o t h e tr e at m e nt pr o d uct or 
a d mi nistr ati o n pr oc e d ur e.  O nl y S A E r e p orts w hic h ar e at l e ast p ossi bl y r el at e d t o t h e tr e at m e nt pr o d uct ( as 
d et er mi n e d b y i n v esti g at or) will r e q uir e st o p p a g e of t h e tri al.  R est art of t h e st u d y will b e gi n u p o n a p pr o v al of 
t h e D S M B. 
•  
T hr e e o ut of t h e first 5 p ati e nts pr es e nt wit h u n ex p ect e d s yst e mic i nf ecti o ns or f e v ers li n k e d t o s us p ect e d 
i nf ecti o n.  R est art of t h e st u d y will b e gi n u p o n a p pr o v al of t h e D S M B  
•  
A n a p h yl actic s h oc k or ot h er s e v er e i nj ecti o n r el at e d t oxiciti es i n a n y s u bj ect.  R est art of t h e st u d y will b e gi n 
u p o n a p pr o v al of t h e D S M B.  
 
T h e D S M B will b e pr o vi d e d wit h listi n g s a n d d escri pti v e s u m m ari es of c urr e nt d at a i ncl u di n g all a d v ers e e v e nts o n a 
q u art erl y  b asis.   If,  f or  a n y  r e as o n,  t h e  us e  of  t h e  U S- M S C  is  c o nsi d er e d  u ns af e  or  i n effic aci o us,  t h e  D S M B  c a n  
r ec o m m e n d st o p pi n g t h e st u d y.  If e nr oll m e nt is h alt e d a n d t h e n r est art e d, t h e s a m e r ul es will a p pl y b e gi n ni n g u p o n 
r est art.  
 
R e p orts a n d R ec or ds M a n a g e m e nt 
 
C o nfi d e nti alit y of all r ec or ds i d e ntif yi n g s u bj ects will b e k e pt. R e g ul at or y a ut h oriti es, r e pr es e nt ati v es of t h e I nstit uti o n al 
R e vi e w B o ar d will b e gr a nt e d acc ess t o m e dic al a n d l a b or at or y  r ec or ds f or t h e p ur p os e of v erific ati o n of pr oc e d ur es a n d 
cli nic al tri al d at a wit h o ut vi ol ati n g t h e c o nfi d e nti alit y of s u bj ect’s i nf or m ati o n t o t h e ext e nt p er mitt e d b y a p plic a bl e l a ws 
a n d r e g ul ati o ns.  N o acc ess t o r ec or ds will b e all o w e d ot h er t h a n u n d er t h e a b o v e d efi n e d c o n diti o ns wit h o ut t h e 
si g n e d, writt e n c o ns e nt of t h e s u bj ect or t h e s u bj ect's l e g al r epr es e nt ati v e. T h e r es ults of t his st u d y will b e p u blis h e d i n a 
p e er r e vi e w e d sci e ntific j o ur n al.  N o p ati e nt i d e ntit y i nf or m ati o n will b e i ncl u d e d i n t h e sci e ntific p a p er.  
 
D at a c oll ect e d f or t his st u d y, i ncl u di n g t h e g e n etic t esti n g will b e a n al yz e d a n d st or e d at t h e D RI. Aft er t h e st u d y is 
c o m pl et e d, t h e d e-i d e ntifi e d, arc hi v e d d at a will b e tr a ns m itt e d t o a n d st or e d at t h e D RI, f or us e b y r es e arc h ers.  
 
Wit h t h e p artici p a nt’s a p pr o v al a n d as a p pr o v e d b y l oc al I n stit uti o n al R e vi e w B o ar ds (I R Bs), d e-i d e ntifi e d bi ol o gic al 
s a m pl es will b e st or e d at t h e D RI. T h es e s a m pl es c o ul d b e us e d t o r es e arc h t h e c a us es of c o vi d- 1 9 or ot h er r el at e d 
i nf ecti o ns, its c o m plic ati o ns a n d ot h er c o n diti o ns f or w hic h i n di vi d u als wit h c o vi d- 1 9 ar e at i ncr e as e d ris k, a n d t o 
i m pr o v e tr e at m e nt. T h e D RI r e p osit or y will als o b e pr o vi d e d wit h a c o d e-li n k t h at will all o w li n ki n g t h e bi ol o gic al 
s p eci m e ns wit h t h e p h e n ot y pic d at a fr o m e ac h p artici p a nt, m ai nt ai ni n g t h e bli n di n g of t h e i d e ntit y of t h e p artici p a nt. 
 
D uri n g t h e c o n d uct of t h e st u d y, a n i n di vi d u al p artici p a nt c a n c h o os e t o wit h dr a w c o ns e nt t o h a v e bi ol o gic al s p eci m e ns 
st or e d f or f ut ur e r es e arc h. H o w e v er, wit h dr a w al of c o ns e nt wit h r e g ar d t o bi os a m pl e st or a g e m a y n ot b e p ossi bl e aft er 
t h e st u d y is c o m pl et e d. W h e n t h e st u d y is c o m pl et e d, acc ess t o st u d y d at a a n d/ or s a m pl es will b e pr o vi d e d t hr o u g h t h e 
D RI.  
 
 
T his i n v esti g ati o n al st u d y will f oll o w t h e i n v esti g at or r e p ort  a n d r ec or d k e e pi n g r e q uir e m e nts s p ecifi e d i n 2 1 C F R P art 
3 1 2. T h es e r e q uir e m e nts ar e s u m m ariz e d b el o w.   
 

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I nv esti g at or R ec or ds 
 
Pri or t o p artici p ati o n i n t h e i n v esti g ati o n, t h e i n v esti g at or m ust h a v e f oll o wi n g d oc u m e nt ati o n: 
 
1.  I n v esti g at or A gr e e m e nt, si g n e d b y t h e i nv esti g at or, w hic h lists a n y p h ysici a ns w h o will b e i n v ol v e d i n c o n d ucti n g 
t h e i n v esti g ati o n u n d er t h e dir ecti o n of t h e pri nci p al i n v esti g at or. 
2.  A c o p y of t h e pri m ar y i n v esti g at or’s c urric ul u m vit a e ( C V) as w ell as c o pi es of C Vs f or a n y c o-i n v esti g at ors. 
3.  A l ett er si g n e d b y t h e c h air p ers o n of t h e I nstit uti o n al R e vi e w B o ar d (I R B), i n dic ati n g t h at t h e I R B h as r e vi e w e d 
a n d a p pr o v e d t his i n v esti g ati o n al pl a n. 
4.  A c o p y of t h e I R B- a p pr o v e d i nf or m e d c o ns e nt d oc u m e nt.   
5.  D uri n g t h e st u d y, i n v esti g at ors ar e r e q uir e d t o m ai nt ai n o n fil e t h e f oll o wi n g acc ur at e, c o m pl et e a n d c urr e nt 
r ec or ds r el ati n g t o t his st u d y — a s u m m ar y of t h es e r ec or ds is d escri b e d b el o w: 
6.  All c orr es p o n d e nc e a n d r e q uir e d r e p orts w hic h p ert ai n t o t h e st u d y; 
7.  R ec or ds of r ec ei pt, us e or dis p ositi o n of t h e I P, i ncl u di n g t h e l ot n u m b er, t h e n a m es of all p ers o ns w h o r ec ei v e d, 
us e d or dis p os e d of a n y pr o d uct will b e m ai nt ai n e d t hr o u g h o ut t h e st u d y at t h e D RI-c G M P f acilit y. 
8.  R ec or ds of e ac h s u bj ect’s c as e hist or y a n d ex p os ur e t o t h e pr o d uct of U C- M S C c ells.  
9.  Si g n e d a n d d at e d c o ns e nt f or ms; 
1 0.  R el e v a nt o bs er v ati o ns, i ncl u di n g r ec or ds c o nc er ni n g a d v e rs e e v e nts, c o n diti o n of e ac h s u bj ect u p o n e nt eri n g 
a n d r es ults of di a g n ostic t ests; 
1 1.  C as e r e p ort f or ms a n d c orr ecti o ns t o t h e f or ms; 
1 2.  Pr ot oc ols a n d a m e n d m e nts; 
1 3.  S u bj ect r ecr uiti n g m at eri als. 
 
I nv esti g at or R e p orts 
 
I n v esti g at ors ar e r e q uir e d t o pr e p ar e a n d s u b mit t o t h e I R B t h e f oll o wi n g c o m pl et e, acc ur at e, a n d ti m el y r e p orts o n t his 
i n v esti g ati o n w h e n n ec ess ar y. T h es e r e p orts i ncl u d e: 
 
1.  T h e i n v esti g at or will n otif y t h e I R B, of a s u bj ect d e at h o cc urri n g r el at e d t o t h e I P d uri n g t h e i n v esti g ati o n as s o o n 
as p ossi bl e-- pr ef er a bl y wit hi n 2 4 h o urs of l e ar ni n g of t h e s u bj ect’s d e at h, b ut i n n o e v e nt l at er t h a n 2 4 h o urs. 
2.  T h e i n v esti g at or will n otif y t h e I R B of a n y u n a ntici p at e d a d v ers e eff ect as s o o n as p ossi bl e, b ut n o l at er t h a n 1 0 
w or ki n g d a ys aft er t h e i n v esti g at or first l e ar ns of t h e eff ect. 
3.  T h e i n v esti g at or will pr o vi d e c urr e nt pr o gr ess r e p orts t o t h e r e vi e wi n g I R B at r e g ul ar i nt er v als a n d at l e ast o n a n 
a n n u al b asis.  
4.  T h e i n v esti g at or will n otif y t h e I R B of a n y d e vi ati o n fr o m  t h e i n v esti g ati o n al pr ot oc ol u n d ert a k e n t o pr ot ect t h e 
lif e a n d p h ysic al w ell- b ei n g of a s u bj ect i n a n e m er g e nc y as s o o n as p ossi bl e, b ut n o l at er t h a n 5 w or ki n g d a ys 
aft er t h e e m er g e nc y occ urr e d. 
5.  T h e i n v esti g at or will n otif y t h e r e vi e wi n g I R B t h at a n i n f or m e d c o ns e nt w as n ot o bt ai n e d fr o m a s u bj ect as s o o n 
as p ossi bl e, b ut n o l at er t h a n 5 w or ki n g d a ys aft er s uc h a n occ urr e nc e. 
6.  T h e i n v esti g at or will pr o vi d e t o t h e I R B a fi n al s u m m a r y r e p ort acc or di n g t o i nstit uti o n al p olici es.  
7.  T h e i n v esti g at or will pr o vi d e a n y ot h er i nf or m ati o n r e q u est e d b y t h e I R B. 
 
D at a C oll ecti o n:  
 
D uri n g e ac h s u bj ect’s visit t o t h e cli nic, or visit vi a T el e H e alt h / p h o n e c all, a n i n v esti g at or p artici p ati n g i n t h e st u d y will 
r ec or d pr o gr ess n ot es t o d oc u m e nt all si g nific a nt o bs er v ati o ns a n d cli nic al r e p orts wit h t h e ori gi n al d oc u m e nts.  All 
i nf or m ati o n h o us e d i n t h e s o urc e d oc u m e nts will b e tr a ns p os e d usi n g el ectr o nic c as e r e p ort f or ms. I n a d diti o n, a n y 
c o nt act  wit h  t h e  s u bj ect  vi a  t el e p h o n e  or  ot h er  m e a ns  t h at  pr o vi d es  si g nific a nt  cli nic al  i nf or m ati o n  will  als o  b e  
d oc u m e nt e d i n t h e pr o gr ess n ot es as d escri b e d a b o v e. D at a g e n er at e d fr o m t h e cli nic al tri al will b e p u blis h e d i n p e er 
r e vi e w e d j o ur n als a n d c o m m u nic at e d wit h r e g ul at or y a ut h oriti es. 

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C o nfi de ntial
  
 
A n y c h a n g es t o i nf or m ati o n i n t h e st u d y pr o gr ess n ot es, ot h er s o urc e d oc u m e nts, a n d c as e r e p ort f or ms will b e i niti al e d 
a n d d at e d i n i n k o n t h e d a y t h e c h a n g e is m a d e b y a sit e st u d y st aff m e m b er a ut h oriz e d t o m a k e t h e c h a n g e. C h a n g es 
will b e m a d e b y stri ki n g a si n gl e li n e t hr o u g h err o n e o us d at a a n d cl e arl y e nt eri n g t h e c orr ect d at a, ( e. g., ri g ht d at a).  If 
t h e  r e as o n  f or  t h e  c h a n g e  is  n ot  a p p ar e nt,  a  bri ef  ex pl a n ati o n  f or  t h e  c h a n g e  will  b e  writt e n  i n  t h e  s o urc e  
d oc u m e nt ati o n b y t h e cli nici a n. 
 
S o urc e D oc u m e nts 
 
S o urc e d oc u m e nts ar e d efi n e d as t h e r es ults of ori gi n al o bs er v ati o ns a n d acti viti es of a cli n ic al i n v esti g ati o n.  S o urc e 
d oc u m e nts will i ncl u d e, b ut ar e n ot li mit e d t o, pr o gr ess n ot es, el ectr o nic d at a, c o m p ut er pri nt o uts, scr e e ni n g l o gs, a n d 
r ec or d e d d at a fr o m a ut o m at e d i nstr u m e nts. All s o urc e d oc u m e nts p ert ai ni n g t o t his st u d y will b e m ai nt ai n e d b y t h e 
i n v esti g at ors a n d m a d e a v ail a bl e f or i ns p ecti o n b y a ut h oriz e d p ers o ns.  
  
R ec or ds R et e nti o n at t h e St u dy Sit e 
 
T h e i n v esti g at or is r es p o nsi bl e f or r et ai ni n g t h e n ec ess ar y r ec or d s. T his i ncl u d es a c o p y of t h e pr ot oc ol, t h e l a b eli n g, c as e 
r e p ort  f or ms,  m e dic al  r ec or ds, ori gi n al  t est  r es ult  r e p ort s,  all  st u d y-r el at e d  c orr es p o n d e nc e,  a  r ec or d  of  writt e n  
i nf or m e d c o ns e nt, a n d a n y ot h er d oc u m e nts p ert ai ni n g t o t h e c o n d uct of t his st u d y.   
 
All i n v esti g at ors p artici p ati n g i n i n v esti g ati o n al st u di es ar e r e q uir e d t o m ai nt a i n d et ail e d cli nic al r ec or ds d uri n g t h e 
i n v esti g ati o n a n d f or a p eri o d of at l e ast t w o y ears aft er t h e l att er of t h e f oll o wi n g t w o d at es: 
T h e d at e o n w hic h t h e i n v esti g ati o n is t er mi n at e d or c o m pl et e d; or, 
T h e d at e t h e r ec or ds ar e n o l o n g er r e q uir e d f or p ur p os es of s u p p orti n g a pr e m ar k et a p pr o v al a p plic ati o n. 
 
P ay m e nt a n d R e m u n er ati o n 
 
N o c o m p e ns ati o n will b e pr o vi d e d t o p ati e nts 
 
C osts 
 
S u bj ects  will  n ot  p a y  t h e  i n v esti g ati o n al  tr e at m e nt  usi n g  U C- M S Cs  n or  f or  t h e  ass oci at e d  c osts  of  pr oc essi n g  or  
tr a ns p ort ati o n of t h e c ells.  
 
 
D at a M a n a g e m e nt : T h e Cli nic al Sit e will m ai nt ai n t h e hi g h est d e gr e e of c o nfi d e nti alit y f or t h e cli nic al a n d r es e arc h 
i nf or m ati o n o bt ai n e d fr o m st u d y s u bj ects. M e dic al a n d r es e arc h r ec or ds will b e m ai nt ai n e d i n t h e strict est c o nfi d e nc e. 
All d at a will b e r e vi e w e d p eri o dic all y b y t h e cli nic al r es e arc h m o nit ors ( C R O R S), D at a S a f et y M o nit ori n g B o ar d ( D S M B), 
a n d I R B of r ec or d. As p art of t h e q u alit y ass ur a nc e a n d l e g al r es p o nsi biliti es of a n i n v esti g ati o n, t h e Cli nic al Sit e will 
p er mit a ut h oriz e d r e pr es e nt ati v es of t h e St u d y PI, i ncl u di n g m e dic al m o nit or, D S M B, I R B, C R O R S, R C Q A a n d h e alt h 
a ut h oriti es t o ex a mi n e- a n d w h e n r e q uir e d b y a p plic a bl e l a w, t o c o p y- cli nic al r ec or ds f or q u alit y ass ur a nc e r e vi e ws, 
a u dits, a n d e v al u ati o ns of t h e st u d y s af et y a n d pr o gr ess. U nl ess r e q uir e d b y t h e l a ws t h at p er mit c o p yi n g of r ec or ds, 
o nl y t h e c o d e d i d e ntit y ass oci at e d wit h d oc u m e nts or wit h s u bj ect d at a m a y b e c o pi e d, wit h all p ers o n all y i d e ntif yi n g 
i nf or m ati o n o bsc ur e d. A ut h oriz e d r e pr es e nt ati v es ar e b o u n d t o m ai nt ai n strict c o nfi d e nti alit y of m e dic al a n d r es e arc h 
i nf or m ati o n li n k e d t o st u d y s u bj ects.  
 
St atistic al A n alysis  

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C o nfi de ntial
  
D escri pti v e a n al ysis of b as eli n e c h ar act eristics t o e v al u at e  diff er e nc es i n a g e, g e n d er, a n d dis e as e s e v erit y b et w e e n 
tr e at m e nt gr o u ps.  W e ex p ect gr o u ps will b e b al a nc e d wit h r es p ect t o dis e as e s e v erit y as w e will e m pl o y str atifi e d 
r a n d o miz ati o n, b as e d o n dis e as e s e v erit y. 
 
Pri m ar y E n d p oi nt: T h e pri m ar y o utc o m e of t his st u d y is t h e s af et y of U C- M S C t h er a p y i n p ati e nts wit h A R D S d u e t o 
C O VI D- 1 9, as ass ess e d b y t h e n u m b er of A Es a n d S A Es as d esc ri b e d i n st u d y e n d p oi nt s ecti o n.  T his a n al ysis will c o m p ar e 
A Es a n d S A Es b et w e e n gr o u ps usi n g Fis h er’s ex act t est.  At t h e mi d p oi nt of st u d y e nr oll m e nt, if t h er e ar e si g nific a ntl y 
m or e A Es i n t h e ex p eri m e nt al ar m b as e d o n Fis h er’s ex act t e st, e arl y t er mi n ati o n will b e c o nsi d er e d b y t h e i n d e p e n d e nt 
d at a s af et y m o nit ori n g b o ar d ( D S M B). 
 
Effic ac y E n d p oi nt:  W e will esti m at e a n d pr o vi d e c o nfi d e nc e i nt er v als f or diff er e nc es i n s ur vi v al, v e ntil at or-fr e e d a ys as 
w ell as t h e v al u es f or P a O 2/ FI O 2, l u n g c o m pli a nc e, a n d ot h e r r el e v a nt r es pir at or y a n d ot h er v ari a bl es, d escri b e d i n st u d y 
e n d p oi nt s ecti o n.  D escri pti v e a n al ysis s uc h as esti m at es of  m e a ns, st a n d ar d d e vi ati o ns, a n d c orr es p o n di n g c o nfi d e nc e 
li mits f or diff er e nc es b et w e e n gr o u ps f or e ac h v ari a bl e u n d er c o nsi d er ati o n will b e c alc ulat e d a n d r e p ort e d f or e ac h 
f oll o w- u p visit. T his will pr o vi d e f urt h er u n d erst a n di n g of i mm u n ol o gic m ec h a nis ms i n v ol v e d i n U C- M S C acti o n o n l u n g 
tiss u e r e p air f oll o wi n g critic al C O VI D- 1 9 dis e as e ass oci at e d wit h A R D S. W e will i nf or m t h e eff ects of U C- M S C i n t his 
p o p ul ati o n, a n d h o w t h at m a y b e aff ect e d b y dis e as e s e v eri t y.  Esti m at es of effic ac y as w ell as v ari a bilit y will b e 
pr o vi d e d, w hic h will b e us ef ul i n d esi g ni n g a l ar g er c o ntr oll e d c o m p ar ati v e tri al. 
 
S a m pl e Siz e C o nsi d er ati o ns:  
T his is a Pil ot i n v esti g ati o n d esi g n e d t o o bt ai n e v al u at e s af et y a n d o bt ai n a n esti m at e of effic ac y of t h e U C- M S C t h er a p y 
t h e  C O VI D- 1 9  p ati e nts  wit h  A R D S.  S a m pl e  siz e  c alc ul ati o ns  ar e  n ot  s e nsi bl e  i n  t his  s etti n g  as  o ur  g o al  is  t o  g ai n  
u n d erst a n di n g of t h e distri b uti o n al pr o p erti es of t h e o utc o m es u n d er c o nsi d er ati o n i n t his gr o u p a n d wit hi n c at e g ori es 
of dis e as e s e v erit y, a n d est a blis h if t h er e is e vi d e nc e of e ffic ac y w hic h w o ul d g ui d e f urt h er i n v esti g ati o ns. D at a i n dic at es 
t h at a p pr oxi m at el y 1 0- 1 1 % of t h e p ati e nts di a g n os e d wit h C O VI D- 1 9 d e v el o p s eri o us c o m plic ati o ns a n d n e e d t o b e 
h os pit aliz e d. M or e t h a n 1 o ut of e v er y 4 h os pit aliz e d C O VI D- 1 9 p ati e nts r e q uir e a d missi o n t o t h e I C U f or r es pir at or y 
s u p p ort, a n d t h os e t h at pr o gr ess t o A R D S ex p eri e nc e 4 3 % m ort alit y r at e. M e as ur es r e g ar di n g st u d y m e a n o utc o m es a n d 
v ari a bilit y c a n b e us e d t o d esi g n a l ar g er, r a n d o miz e d, c o ntr oll e d cli nic al tri al t o t est diff er e nc es i n effic ac y b et w e e n 
s e v er al gr o u ps.  E n d p oi nt d at a s h o ul d b e a v ail a bl e f or all e nr oll e d s u bj ects. A n exc e pti on will b e o nl y if d e at h occ urs or if 
t h e s u bj ects wit h dr a ws c o ns e nt t o b e f oll o w e d, alt h o u g h w e ex p ect t his li mit e d or n o n- exist e nt i n C O VI D- 1 9 p ati e nts.  
 
St u dy Or g a niz ati o n a n d A d mi nistr ati o n : Dr. Ric or di, Dr. Al ej a n dr o a n d Dr. B ai d al will h a v e t h e r es p o nsi bilit y of 
o v ers e ei n g,  st e eri n g,  a n d  m a n a gi n g  t h e  o v er all  dir ecti o n  of  t his  tri al  will  b e  acc o u nt a bl e  f or  k e y  t as ks  a n d  st u d y  
d eli v er a bl es. W or ki n g cl os el y wit h Dr. Al v ar ez, w h o will o v ers e e s u bj ect r ecr uit m e nt, tr e at m e nt, st a n d ar d- of-c ar e, a n d 
f oll o w- u p, t h e y will ass ur e t h at all p ers o n n el i n v ol v e d i n t h e st u d y ar e a p pr o pri at el y tr ai n e d, t h e st u d y is i niti at e d a n d 
c o n d uct e d  as  o utli n e d  i n  t h e  Cli nic al  Pr ot oc ol,  a n d  i n  acc or d a nc e  wit h  a p plic a bl e  r e g ul ati o ns.  All  s u bj ects  will  b e  
r ecr uit e d at t h e  i nt e nsi v e c ar e u nits of t h e H os pit als, a n d will b e tr e at e d a n d f oll o w e d- u p t h er e. A n i n d e p e n d e nt 
M e dic al M o nit or a n d D S M B will m o nit or st u d y pr o gr ess a n d r e vi e w all A Es/ S A Es r e g ul arl y, i ncl u di n g e v e nts t h at mi g ht 
r es ult i n disc o nti n u ati o n of t h e st u d y. Mr. J u a n P er ez- Sc h olz will act as t h e st u d y Fi n a nci al A d mi nistr at or. St u d y C o-Is will 
ass ur e s m o ot h c o n d uct of t h e tri al t h at i ncl u d es ti m el y ex ec ut e d m ec h a nistic st u di es, h a n dli n g p ati e nt s a m pl es, d at a 
i nt e grit y, a n d d at a a n al ysis. Dr. Li n ets k y will ass ur e U C- MS C Fi n al Pr o d uct is m a n uf act ur e d as m a n d at e d b y a p plic a bl e 
st a n d ar d a n d r e g ul ati o ns, st u d y I N D a n d S O Ps. St u d y C o or di n at or will b e r es p o nsi bl e f or d ay-t o- d a y ex ec uti o n of t h e 
st u d y a n d will r e p ort t o Dr. Ric or di, Dr. Al ej a n dr o or Dr. B ai d al. 
 

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C o nfi de ntial
  
 
D at a M a n a g e m e nt  M ec h a nistic st u di es will b e p erf or m e d at t h e D RI, U M. T h e sit e will m ai nt ai n t h e hi g h est d e gr e e of 
c o nfi d e nti alit y f or t h e cli nic al a n d r es e arc h i nf or m ati o n o bt a i n e d fr o m st u d y s u bj ects. M e dic al a n d r es e arc h r ec or ds will 
b e m ai nt ai n e d i n t h e strict est c o nfi d e nc e. All d at a will b e r e vi e w e d p eri o dic all y b y t h e cli nic al m o nit ors ( C R O R S), D at a 
S af et y M o nit ori n g B o ar d ( D S M B), a n d I R B of r ec or d. As p art  of t h e q u alit y ass ur a nc e a n d l e g al r es p o nsi biliti es of a n 
i n v esti g ati o n, t h e Cli nic al Sit e will p er mit a ut h oriz e d r e pres e nt ati v es of t h e St u d y PI, i ncl u di n g m e dic al m o nit or, D S M B, 
I R B, C R O R S, R es e arc h C o m pli a nc e a n d Q ualit y Ass ur a nc e ( R C Q A) a n d h e alt h a ut h oriti es t o ex a mi n e- a n d w h e n r e q uir e d 
b y a p plic a bl e l a w, t o c o p y- cli nic al r ec or ds f or q u alit y ass ur a nc e r e vi e ws, a u dits, a n d e v al u ati o ns of t h e st u d y s af et y a n d 
pr o gr ess. U nl ess r e q uir e d b y t h e l a ws t h at p er mit c o p yi n g of r ec or ds, o nl y t h e c o d e d i d e ntit y ass oci at e d wit h d oc u m e nts 
or wit h s u bj ect d at a m a y b e c o pi e d, wit h all p ers o n all y i d e ntif yi n g i nf or m ati o n o bsc ur e d. A ut h oriz e d r e pr es e nt ati v es ar e 
b o u n d t o m ai nt ai n strict c o nfi d e nti alit y of m e dic al a n d r es e arc h i nf or m ati o n li n k e d t o st u d y s u bj ects.   
 
 
R e g ul at ory, Et hic al, a n d St u dy Ov ersi g ht C o nsi d er ati o ns 
 
C o ns e nt f or ms d escri bi n g i n d et ail t h e st u d y i nt er v e nti o n, st u d y pr oc e d ur es, a n d ris ks ar e gi v e n t o t h e p artici p a nt a n d 
writt e n d oc u m e nt ati o n of i nf or m e d c o ns e nt is r e q uir e d pri or t o st arti n g i nt er v e nti o n/ a d mi nist eri n g st u d y i nt er v e nti o n.  
T h e c o ns e nt m at eri als ar e s u b mitt e d wit h t his pr ot oc ol.  
 
I nf or m e d c o ns e nt is a pr oc ess t h at is i niti at e d pri or t o t h e i n di vi d u al’s a gr e ei n g t o p artici p at e i n t h e st u d y a n d c o nti n u es 
t hr o u g h o ut t h e i n di vi d u al’s st u d y p artici p ati o n. C o ns e nt f or ms will b e I nstit uti o n al R e vi e w B o ar d (I R B)- a p pr o v e d a n d t h e 
p artici p a nt will b e as k e d t o r e a d a n d r e vi e w t h e d oc u m e nt . T h e i n v esti g at or will ex pl ai n t h e r es e arc h st u d y t o t h e 
p artici p a nt/ pr ox y  r e m ot el y (vi a p h o n e or z o o m) a n d a ns w er a n y q u esti ons t h at m a y aris e. A v er b al ex pl a n ati o n will b e 
pr o vi d e d i n t er ms s uit e d t o t h e p artici p a nt’s c o m pr e h e nsi o n of t h e p ur p os es, pr oc e d ur es, a n d p ot e nti al ris ks of t h e 
st u d y a n d of t h eir ri g hts as r es e arc h p artici p a nts.  P artici pa nts or its d esi g n e e (l e g all y a ut h oriz e d r e pr es e nt ati v e) will 
h a v e t h e o p p ort u nit y t o c ar ef ull y r e vi e w t h e writt e n c o ns e n t f or m a n d as k q u esti o ns pri or t o si g ni n g. T h e p artici p a nts 
s h o ul d h a v e t h e o p p ort u nit y t o disc uss t h e st u d y wit h t h eir f a mil y or s urr o g at es or t hi n k a b o ut it pri or t o a gr e ei n g t o 
p artici p at e. T h e p artici p a nt will si g n t h e i nf or m e d c o ns e nt d oc u m e nt pri or t o a n y pr oc e d ur es b ei n g d o n e s p ecific all y f or 
t h e st u d y. P artici p a nts m ust b e i nf or m e d t h at p artici p ati o n is v ol u nt ar y a n d t h at t h e y m a y wit h dr a w fr o m t h e st u d y at 
a n y ti m e, wit h o ut pr ej u dic e. A c o p y of t h e i nf or m e d c o ns e nt d oc u m e nt will b e gi v e n t o t h e p artici p a nts f or t h eir r ec or ds. 
T h e i nf or m e d c o ns e nt pr oc ess will b e c o n d uct e d a n d d oc u m e nt e d  i n t h e s o urc e d oc u m e nt (i ncl u di n g t h e d at e), a n d t h e 
f or m si g n e d, b ef or e t h e p artici p a nt u n der g o es a n y st u d y-s p ecific pr oc e d ur es. T h e I C F will b e u pl o a d e d t o t h e p ati e nt’s 
el ectr o nic m e dic al r ec or d. T h e ri g hts a n d w elf ar e of t h e p artic i p a nts will b e pr ot ect e d b y e m p h asizi n g t o t h e m t h at t h e 
q u alit y of t h eir m e dic al c ar e will n ot b e a d v ers el y aff e ct e d if t h e y d ecli n e t o p artici p at e i n t his st u d y. 
 
St u dy Disc o nti n u ati o n a n d Cl os ur e 
 
T his st u d y m a y b e t e m p or aril y s us p e n d e d or pr e m at ur el y t er m i n at e d if t h er e is s uffici e nt r e as o n a bl e c a us e.  Writt e n 
n otific ati o n, d oc u m e nti n g t h e r e as o n f or st u d y s us p e nsi o n or t er mi n ati o n, will b e pr o vi d e d b y t h e s us p e n di n g or 
t er mi n ati n g p art y t o t h e I R B, F D A, D S M B, a n d ot h er o v ersi g ht a n d r e g ul at or y a ut h oriti es.  If t h e st u d y is pr e m at ur el y 
t er mi n at e d or s us p e n d e d, t h e Pri nci p al I n v esti g at or ( PI) will pr o m ptl y i nf or m st u d y p artici p a nts, t h e I nstit uti o n al R e vi e w 
B o ar d (I R B), a n d s p o ns or a n d will pr o vi d e t h e r e as o n(s) f or t h e t er mi n ati o n or s u s p e nsi o n.  St u d y p artici p a nts will b e 
c o nt act e d, as a p plic a bl e, a n d b e i nf or m e d of c h a n g es t o st u d y visit sc h e d ul e. 
  
Circ u mst a nc es t h at m a y w arr a nt t er mi n ati o n or s us p e nsi o n i ncl u d e, b ut ar e n ot li mit e d t o: 
•  
D et er mi n ati o n of u n ex p ect e d, si g nific a nt, or u n acc e pt a bl e ris k t o p artici p a nts 
•  
D e m o nstr ati o n of effic ac y t h at w o ul d w arr a nt st o p pi n g    

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C o nfi de ntial
  
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I ns uffici e nt c o m pli a nc e t o pr ot oc ol r e q uir e m e nts 
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D at a t h at ar e n ot s uffici e ntl y c o m pl et e a n d/ or e v al u a bl e 
•  
D et er mi n ati o n t h at t h e pri m ar y e n d p oi nt h as b e e n m et 
•  
D et er mi n ati o n of f utilit y 
 
St u d y m a y r es u m e o nc e c o nc er ns a b o ut s af et y, pr ot oc ol c o m pli a nc e, a n d d at a q u alit y ar e a d dr ess e d, a n d s atisf y t h e 
s p o ns or, I R B a n d/ or F o o d a n d Dr u g A d mi nistr ati o n ( F D A).] 
 
C o nfi d e nti ality a n d Priv acy  
 
P artici p a nt c o nfi d e nti alit y a n d pri v ac y is strictl y h el d i n tr ust b y t h e p artici p ati n g i n v esti g at ors, t h eir st aff, a n d t h e 
s p o ns or(s) a n d t h eir i nt er v e nti o ns. T his c o nfi d e nti alit y is ext e n d e d t o c o v er t esti n g of bi ol o g ic al s a m pl es i n a d diti o n t o 
t h e cli nic al i nf or m ati o n r el ati n g t o p artici p a nts. T h er ef ore, t h e st u d y pr ot oc ol, d oc u m e nt ati o n, d at a, a n d all ot h er 
i nf or m ati o n g e n er at e d will b e h el d i n strict c o nfi d e nc e. N o i nf or m ati o n c o nc er ni n g t h e st u d y or t h e d at a will b e r el e as e d 
t o a n y u n a ut h oriz e d t hir d p art y wit h o ut pri or writt e n a p pr o v al of t h e s p o ns or.  
 
All r es e arc h acti viti es will b e c o n d uct e d i n t h e e m er g e nc y r o o m a n d/ or i nt e nsi v e c ar e u nit, as pri v at e a s etti n g as 
p ossi bl e. 
 
T h e st u d y m o nit or, ot h er a ut h oriz e d r e pr es e nt ati v es of t h e s p o ns or, r e pr es e nt ati v es of t he I nstit uti o n al R e vi e w B o ar d 
(I R B), r e g ul at or y a g e nci es or p h ar m ac e utic al c o m p a n y s u p plyi n g st u d y pr o d uct m a y i ns p ect all d oc u m e nts a n d r ec or ds 
r e q uir e d t o b e m ai nt ai n e d b y t h e i n v esti g at or, i ncl u di n g b ut n ot li mit e d t o, m e dic al r ec or ds ( offic e, cli nic, or h os pit al) 
a n d p h ar m ac y r ec or ds f or t h e p artici p a nts  i n t his st u d y. T h e cli nic al st u d y sit e will p er mit acc ess t o s uc h r ec or ds. 
 
T h e st u d y p artici p a nt’s c o nt act i nf or m ati o n will b e s ec ur el y st or e d at e ac h cli nic al sit e f or i nt er n al us e d uri n g t h e st u d y. 
At t h e e n d of t h e st u d y, all r ec or ds will c o nti n u e t o b e k e pt i n a s ec ur e l oc ati o n f or as l o n g a p eri o d as dict at e d b y t h e 
r e vi e wi n g I R B, I nstit uti o n al p olici es, or s p o ns or r e q uir e m e nts. 
 
St u d y p artici p a nt r es e arc h d at a, w hic h is f or p ur p os es of st atis tic al a n al ysis a n d sci e ntific r e p orti n g, will b e tr a ns mitt e d 
t o a n d st or e d at t h e D RI. T his will n ot i ncl u d e t h e p artici p a nt’s c o nt act or i d e ntif yi n g i nf or m ati o n. R at h er, i n di vi d u al 
p artici p a nts a n d t h eir r es e arc h d at a will b e i d e ntifi e d b y a u ni q u e st u d y i d e ntific ati o n n u m b er. T h e st u d y d at a e ntr y a n d 
st u d y m a n a g e m e nt s yst e ms us e d b y cli nic al sit es a n d b y t he r es e arc h st aff will b e s ec ur e d a n d p ass w or d pr ot ect e d. At 
t h e e n d of t h e st u d y, all st u d y d at a b as es will b e d e-i d e ntifi e d a n d arc hi v e d at t h e D RI. 
 
P artici p a nt c o nfi d e nti alit y a n d pri v ac y is strictl y h el d i n tr ust b y t h e p artici p ati n g i n v esti g at ors, t h eir st aff, a n d t h e 
s p o ns or(s) a n d t h eir i nt er v e nti o ns. T his c o nfi d e nti alit y is ext e n d e d t o c o v er t e sti n g of bi ol o gic al s a m pl es a n d g e n etic 
t ests i n a d diti o n t o t h e cli nic al i nf or m ati o n r el ati n g t o p artici p a nts. T h er ef or e, t h e st u d y pr ot oc ol, d oc u m e nt ati o n, d at a, 
a n d all ot h er i nf or m ati o n g e n er at e d will b e h el d i n strict c o nfi d e nc e. N o i nf or m ati o n c o nc er ni n g t h e st u d y or t h e d at a 
will b e r el e as e d t o a n y u n a ut h oriz e d t hir d p art y wit h o ut pri or writt e n a p pr o v al of t h e s p o ns or.  
 
All r es e arc h acti viti es will b e c o n d uct e d i n as pri v at e a s etti n g as p ossi bl e. 
 
T h e st u d y m o nit or, ot h er a ut h oriz e d r e pr es e nt ati v es of t h e s p o ns or, r e pr es e nt ati v es of t he I nstit uti o n al R e vi e w B o ar d 
(I R B), r e g ul at or y a g e nci es or p h ar m ac e utic al c o m p a n y s u p plyi n g st u d y pr o d uct m a y i ns p ect all d oc u m e nts a n d r ec or ds 
r e q uir e d t o b e m ai nt ai n e d b y t h e i n v esti g at or, i ncl u di n g b ut n ot li mit e d t o, m e dic al r ec or ds ( offic e, cli nic, or h os pit al) 
a n d p h ar m ac y r ec or ds f or t h e p artici p a nts  i n t his st u d y. T h e cli nic al st u d y sit e will p er mit acc ess t o s uc h r ec or ds. 
 
T h e st u d y p artici p a nt’s c o nt act i nf or m ati o n will b e s ec ur el y st or e d at e ac h cli nic al sit e f or i nt er n al us e d uri n g t h e st u d y. 
At t h e e n d of t h e st u d y, all r ec or ds will c o nti n u e t o b e k e pt i n a s ec ur e l oc ati o n f or as l o n g a p eri o d as dict at e d b y t h e 
r e vi e wi n g I R B, I nstit uti o n al p olici es, or s p o ns or r e q uir e m e nts. 

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C o nfi de ntial
  
 
St u d y p artici p a nt r es e arc h d at a, w hic h is f or p ur p os es of st atis tic al a n al ysis a n d sci e ntific r e p orti n g, will b e tr a ns mitt e d 
t o a n d st or e d at t h e D RI. T his will n ot i ncl u d e t h e p artici p a nt’s c o nt act or i d e ntif yi n g i nf or m ati o n. R at h er, i n di vi d u al 
p artici p a nts a n d t h eir r es e arc h d at a will b e i d e ntifi e d b y a u ni q u e st u d y i d e ntific ati o n n u m b er. T h e st u d y d at a e ntr y a n d 
st u d y m a n a g e m e nt s yst e ms us e d b y cli nical sit es a n d b y D RI r es e arc h st aff will b e s ec ur e d a n d p ass w or d pr ot ect e d. At 
t h e e n d of t h e st u d y, all st u d y d at a b as es will b e d e-i d e ntifi e d a n d arc hi v e d at t h e D RI. 
 
 
 
F ut ur e Us e of St or e d S p eci m e ns a n d D at a  
 
D at a c oll ect e d f or t his st u d y will b e a n al yz e d a n d st or e d at t h e D RI. G e n etic t esti n g will b e c o n d uct e d as d et ail e d i n t h e 
sc h e d ul e of ass ess m e nt. Aft er t h e st u d y is c o m pl et e d, t h e d e-i d entifi e d, arc hi v e d d at a will b e tr a ns mitt e d t o a n d st or e d 
at t h e D RI, f or us e b y ot h er r es e arc h ers i ncl u di n g t h os e o utsi d e of t h e st u d y. P er missi o n t o tr a ns mit d at a t o t h e 
c oll a b or at ors will b e i ncl u d e d i n t h e i nf or m e d c o ns e nt.  
 
Wit h t h e p artici p a nt’s a p pr o v al a n d as a p pr o v e d b y l oc al I n stit uti o n al R e vi e w B o ar ds (I R Bs), d e-i d e ntifi e d bi ol o gic al 
s a m pl es will b e st or e d at t h e D RI wit h t h e s a m e g o al as t he s h ari n g of d at a wit h t h e c o ll a b or at ors. T h es e s a m pl es c o ul d 
b e us e d t o r es e arc h t h e c a us es of C O VI D- 1 9, its c o m plic ati o ns a n d ot h er c o n diti o ns f or w hic h i n di vi d u als wit h vir al 
i nf ecti o ns ar e at i ncr e as e d ris k, a n d t o i m pr o v e tr e at m e nt. T he D RI will als o b e pr o vi d e d wit h a c o d e-li n k t h at will all o w 
li n ki n g t h e bi ol o gic al s p eci m e ns wit h t h e p h e n ot y pic d at a fr o m e ac h p artici p a nt, m ai nt ai ni n g t h e bli n di n g of t h e i d e ntit y 
of t h e p artici p a nt. 
 
D uri n g t h e c o n d uct of t h e st u d y, a n i n di vi d u al p artici p a nt c a n c h o os e t o wit h dr a w c o ns e nt t o h a v e bi ol o gic al s p eci m e ns 
st or e d f or f ut ur e r es e arc h. H o w e v er, wit h dr a w al of c o ns e nt wit h r e g ar d t o bi os a m pl e st or a g e m a y n ot b e p ossi bl e aft er 
t h e st u d y is c o m pl et e d.  
 
W h e n t h e st u d y is c o m pl et e d, acc ess t o st u d y d at a a n d/ or s a m pl es will b e pr o vi d e d t hr o u g h t h e D RI. 
 
 
S af ety Ov ersi g ht 
S af et y o v ersi g ht will b e u n d er t h e dir ecti o n of a D at a a n d S a f et y M o nit ori n g B o ar d ( D S M B) c o m p os e d of i n di vi d u als wit h 
t h e a p pr o pri at e ex p ertis e.  T h e D S M B will m e et aft er t h e c o m pl eti o n of t h e i nf usi o ns i n t h e first 6 p ati e nts, or as 
dict at e d b y t h e St o p pi n g R ul es e v e nts, q u art erl y t o ass ess s a f et y a n d effic ac y d at a o n e ac h ar m of t h e st u d y. T h e D M S B 
will o p er at e u n d er t h e r ul es of a n a p pr o v e d c h art er t h at will b e writt e n a n d r e vi e w e d at t h e or g a niz ati o n al m e eti n g of 
t h e D S M B. At t his ti m e, e ac h d at a el e m e nt t h at t h e D S M B n e e ds t o ass ess will b e cl e arl y d efi n e d. T h e D S M B will pr o vi d e 
its i n p ut t o t h e st u d y t e a m a n d s p o ns or.  
 
Cli nic al M o nit ori n g 
Cli nic al sit e m o nit ori n g is c o n d uct e d t o e ns ur e t h at t h e ri g hts  a n d w ell- b ei n g of tri al p artici p a nts ar e pr ot ect e d, t h at t h e 
r e p ort e d tri al d at a ar e acc ur at e, c o m pl et e, a n d v erifi a bl e, a n d t h at t h e c o n d uct of t h e tri al is i n c o m pli a nc e wit h t h e 
c urr e ntl y a p pr o v e d pr ot oc ol/ a m e n d m e nt(s), wit h I nt er n ati o n al C o nf er e nc e o n H ar m o n is ati o n G o o d Cli nic al Pr actic e (I C H 
G C P), a n d wit h a p plic a bl e r e g ul at or y r e q uir e m e nt(s).  
 
•  
M o nit ori n g f or t his st u d y will b e p erf or m e d b y C R O R S, a u nit of t h e U M.  
•  
A ris k- b as e d m o nit ori n g pl a n will b e d e v el o p e d b y t h e C R O R S Dir ect or a n d t h e st u d y S p o ns or w hic h will d et ail 
t h e fr e q u e nc y f or m o nit ori n g visits a n d p ar a m et ers t o b e m o nit or e d t hr o u g h o ut t h e st u d y.  
 

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C o nfi de ntial
  
Q u ality Ass ur a nc e a n d Q u ality C o ntr ol 
T h e U M cli nic al sit e will p erf or m i nt er n al q u alit y a n d d at a m a n a g e m e nt of st u d y c o n d uct, d at a a n d bi ol o gic al s p eci m e n 
c oll ecti o n, d oc u m e nt ati o n a n d c o m pl eti o n b y st u d y i n v esti g at ors at t his m ulti-sit e tri al. T h e d at a s af et y m o nit ori n g 
b o ar d f or t his st u d y will als o o v ers e e t h e st u d y a n d m a k e r ec o m m e n d ati o ns.  
 
A n i n di vi d u aliz e d q u alit y m a n a g e m e nt pl a n will b e d e v el o p e d t o d escri b e a sit e’s q u alit y m a n a g e m e nt. 
 
Q u alit y c o ntr ol ( Q C) pr oc e d ur es will b e i m pl e m e nt e d b e gi n ni n g  wit h t h e d at a e ntr y s yst e m a n d d at a Q C c h ec ks t h at will 
b e r u n o n t h e d at a b as e will b e g e n er at e d. A n y missi n g d at a  or d at a a n o m ali es will b e c o m m u nic at e d t o t h e sit e(s) f or 
cl arific ati o n/r es ol uti o n. 
 
 
T h e i nv esti g ati o n al sit e will pr o vi d e dir ect acc ess t o all tr i al r el at e d sit es, s o urc e d at a/ d oc u m e nts, a n d r e p orts f or t h e 
p ur p os e of m o nit ori n g a n d a u diti n g b y t h e s p o ns or, a n d i ns p ecti o n b y l oc al a n d r e g ul at or y a ut h oriti es. 
 
D at a C oll ecti o n a n d M a n a g e m e nt R es p o nsi biliti es  
D at a c oll ecti o n is t h e r es p o nsi bilit y of t h e cli nic al tri al st aff at t h e sit e u n d er t h e s u p er visi o n of t h e sit e i n v esti g at or. T h e 
i n v esti g at or is r es p o nsi bl e f or e ns uri n g t h e acc ur ac y, c o m pl et e n ess, l e gi bilit y, a n d ti m eli n ess of t h e d at a r e p ort e d. 
 
All s o urc e d oc u m e nts s h o ul d b e c o m pl et e d i n a n e at, l e gi bl e m a n n er t o e ns ur e acc ur at e i nt er pr et ati o n of d at a.   
 
St u d y will us e b ot h el ectr o nic m e dic al r ec or ds ( U C h art a n d C e r n er) a n d p a p er t o r ec or d as a s o urc e d oc u m e nt ati o n.  
D at a r ec or d e d i n t h e el ectr o nic c as e r e p ort f or m ( e C R F) d eri v e d fr o m s o urc e d o c u m e nts s h o ul d b e c o nsist e nt wit h t h e 
d at a r ec or d e d o n t h e s o urc e d oc u m e nts.  
 
Cli nic al d at a (i ncl u di n g a d v ers e e v e nts ( A Es), C O VI D- 1 9 r el a t e d s el ect c o nc o mit a nt m e dic atio ns as s p ecifi e d i n t h e C R F, 
a n d ex p ect e d a d v ers e r e acti o ns d at a) a n d cli nic al l a b or at or y  d at a will b e e nt er e d i nt o U M a ut h oriz e d s yst e ms ( 2 1 C F R 
P art 1 1-c o m pli a nt) pr o vi d e d b y t h e U M. T h e d at a s yst e m i ncl u d es p ass w or d pr ot ecti o n a n d i nt er n al q u alit y c h ec ks, s uc h 
as a ut o m atic r a n g e c h ec ks, t o i d e ntif y d a t a t h at a p p e ar i nc o nsist e nt, i nc o m pl et e, or i n acc ur at e. Cli nic al d at a will b e 
e nt er e d dir ectl y fr o m t h e s o urc e d oc u m e nts. 
 
Use of all ot her me dicati o n rec or ds fr o m E M Rs ( U C hart at  U M a n d Cer ner at J H S) will be c ollecte d (e. g. pri nt 
scree n or me dicati o n a d mi nistrati o n rec or d), i nitiale d f or t heir c o m pleti o n of re vie w/assess me nt, a n d sa ve d wit h 
patie nts researc h rec or ds.  
 
St u dy R ec or ds R et e nti o n  
 
St u d y d oc u m e nts s h o ul d b e r et ai n e d f or a mi ni m u m of 2 y e ars aft er t h e l ast a p pr o v al of a m ar k eti n g a p plic ati o n i n a n 
I nt er n ati o n al C o nf er e nc e o n H ar m o nis ati o n (I C H) r e gi o n an d u ntil t h er e ar e n o p e n di n g or c o nt e m pl at e d m ar k eti n g 
a p plic ati o ns i n a n I C H r e gi o n or u ntil at l e ast 2 y e ars h a v e el a ps e d si nc e t h e f or m al disc o nti n u ati o n of cli nic al 
d e v el o p m e nt of t h e st u d y i nt er v e nti o n. T h es e d oc u m e nts s h o ul d  b e r et ai n e d f or a l o n g er p eri o d, h o w e v er, if r e q uir e d b y 
l oc al r e g ul ati o ns. N o r ec or ds will b e d estr o y e d wit h o ut t h e writt e n c o ns e nt of t h e s p o ns or, if a p plic a bl e. It is t h e 
r es p o nsi bilit y of t h e s p o ns or t o i nf or m t h e i n v esti g at or w h e n t h es e d oc u m e nts n o l o n g er n e e d t o b e r et ai n e d.] 
 
 

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C o nfi de ntial
  
 
R ef er e nc es 
1.  
Z h u N, Z h a n g D, W a n g W, Li X, Y a n g B,  S o n g J, Z h a o X, H u a n g B, S hi W, L u R, Ni u P, Z h a n F, M a X, W a n g D, X u W, 
W u G, G a o G F, T a n W, C hi n a N o v el C or o n a vir us I, R es e arc h T. A N o v el C or o n a vir us fr o m P ati e nts wit h P n e u m o ni a i n 
C hi n a, 2 0 1 9. N E n gl J M e d. 2 0 2 0; 3 8 2( 8): 7 2 7- 3 3. E p u b 2 0 2 0/ 0 1/ 2 5. d oi: 1 0. 1 0 5 6/ N EJ M o a 2 0 0 1 0 1 7. P u b M e d P MI D: 
3 1 9 7 8 9 4 5. 
2.  
G u o Y R, C a o Q D, H o n g Z S, T a n Y Y, C h e n S D, Ji n HJ, T a n K S , W a n g D Y, Y a n Y. T h e ori gi n, tr a ns missi o n a n d cli nic al 
t h er a pi es o n c or o n a vir us dis e as e 2 0 1 9 ( C O VI D- 1 9) o ut br e a k - a n u p d at e o n t h e st at us. Mil M e d R es. 2 0 2 0; 7( 1): 1 1. E p u b 
2 0 2 0/ 0 3/ 1 5. d oi: 1 0. 1 1 8 6/s 4 0 7 7 9- 0 2 0- 0 0 2 4 0- 0. P u b M e d P MI D: 3 2 1 6 9 1 1 9. 
3.  
W H O W H O. C or o n a vir us dis e as e ( C O VI D- 1 9) o ut br e a k 2 0 2 0: htt ps:// w w w. w h o.i nt/ e m er g e nci es/ dis e as es/ n o v el-
c or o n a vir us- 2 0 1 9. 
4.  
Z h a n g S, Di a o M, Y u W, P ei L, Li n Z, C h e n D. Esti m ati o n of t h e r e pr o d ucti v e n u m b er of N o v el C or o n a vir us 
( C O VI D- 1 9) a n d t h e pr o b a bl e o ut br e a k siz e o n t h e Di a m o n d Pri nc ess cr uis e s hi p: A d at a- dri v e n a n al ysis. I nt J I nf ect Dis. 
2 0 2 0. E p u b 2 0 2 0/ 0 2/ 2 6. d oi: 1 0. 1 0 1 6/j.iji d . 2 0 2 0. 0 2. 0 3 3. P u b M e d P MI D: 3 2 0 9 7 7 2 5. 
5.  
Z h a o S, Li n Q, R a n J, M us a S S, Y a n g  G, W a n g W, L o u Y, G a o D, Y a n g L, H e D, W a n g M H. Pr eli mi n ar y esti m ati o n of 
t h e b asic r e pr o d ucti o n n u m b er of n o v el c or o n a vir us ( 2 0 1 9- n C o V) i n C hi n a, fr o m 2 0 1 9 t o 2 0 2 0: A d at a- dri v e n a n al ysis i n 
t h e e arl y p h as e of t h e o ut br e a k. I nt J I nf ect Dis. 2 0 2 0; 9 2: 2 1 4- 7. E p u b 2 0 2 0/ 0 2/ 0 3. d oi: 1 0. 1 0 1 6/j.iji d. 2 0 2 0. 0 1. 0 5 0. 
P u b M e d P MI D: 3 2 0 0 7 6 4 3. 
6.  
H u a n g C, W a n g Y, Li X, R e n L, Z h a o J, H u Y, Z h a n g L, F a n G, X u J, G u X, C h e n g Z, Y u T, Xi a J, W ei Y, W u W, Xi e X, 
Yi n W, Li H, Li u M, Xi a o Y, G a o H, G u o L, Xi e J, W a n g G, Ji a n g R, G a o Z, Ji n Q, W a n g J, C a o B. Cli nic al f e at ur es of p ati e nts 
i nf ect e d wit h 2 0 1 9 n o v el c or o n a vir us i n W u h a n, C hi n a. L a nc et. 2 0 2 0; 3 9 5( 1 0 2 2 3): 4 9 7- 5 0 6. E p u b 2 0 2 0/ 0 1/ 2 8. d oi: 
1 0. 1 0 1 6/ S 0 1 4 0- 6 7 3 6( 2 0) 3 0 1 8 3- 5. P u b M e d P MI D: 3 1 9 8 6 2 6 4. 
7.  
W a n g D, H u B, H u C, Z h u F, Li u X, Z h a n g J, W a n g B, Xi a n g H, C h e n g Z, Xi o n g Y, Z h a o Y, Li Y, W a n g X, P e n g Z. 
Cli nic al C h ar act eristics of 1 3 8 H os pit a liz e d P ati e nts Wit h 2 0 1 9 N o v el C or o n a vir us-I nf ect e d P n e u m o ni a i n W u h a n, C hi n a. 
J A M A. 2 0 2 0. E p u b 2 0 2 0/ 0 2/ 0 8. d oi: 1 0.1 0 0 1/j a m a. 2 0 2 0. 1 5 8 5. P u b M e d P MI D: 3 2 0 3 1 5 7 0. 
8.  
C h e n N, Z h o u M, D o n g X, Q u J, G o n g F, H a n Y, Qi u Y, W a n g J, Li u Y, W ei Y, Xi a J, Y u T, Z h a n g X, Z h a n g L. 
E pi d e mi ol o gic al a n d cli nic al c h ar act eristics of 9 9 c as es of 2 0 1 9 n o v el c or o n a vir us p n e u m o ni a i n W u h a n, C hi n a: a 
d escri pti v e st u d y. L a nc et. 2 0 2 0; 3 9 5( 1 0 2 2 3): 5 0 7- 1 3. E p u b  2 0 2 0/ 0 2/ 0 3. d oi: 1 0. 1 0 1 6/ S0 1 4 0- 6 7 3 6( 2 0) 3 0 2 1 1- 7. P u b M e d 
P MI D: 3 2 0 0 7 1 4 3. 
9.  
Gr ass elli G, P es e nti A, C ecc o ni M. Critic al C ar e Utiliz ati o n f or t h e C O VI D- 1 9 O ut br e a k i n L o m b ar d y, It al y: E arl y 
Ex p eri e nc e a n d F or ec ast D uri n g a n E m er g e nc y R es p o n s e. J A M A. 2 0 2 0. E p u b 2 0 2 0/ 0 3/1 4. d oi: 1 0. 1 0 0 1/j a m a. 2 0 2 0. 4 0 3 1. 
P u b M e d P MI D: 3 2 1 6 7 5 3 8. 
1 0.  
W u C, C h e n X, C ai Y, Xi a J, Z h o u X, X u S, H u a n g H, Z h a n g L, Z h o u X, D u C, Z h a n g Y, S o n g J, W a n g S, C h a o Y, Y a n g Z, 
X u J, Z h o u X, C h e n D, Xi o n g W, X u L, Z h o u F, Ji a n g J, B ai C, Z h e n g J, S o n g Y. Ris k F act ors Ass oci at e d Wit h Ac ut e 
R es pir at or y Distr ess S y n dr o m e a n d D e at h i n P ati e nts Wit h C or o n a vir us Dis e as e 2 0 1 9 P n e u m o ni a i n W u h a n, C hi n a. J A M A 
I nt er n M e d. 2 0 2 0. E p u b 2 0 2 0/ 0 3/ 1 4. d oi: 1 0.1 0 0 1/j a m ai nt er n m e d. 2 0 2 0. 0 9 9 4. P u b M e d P MI D: 3 2 1 6 7 5 2 4. 
1 1.  
S hi H, H a n X, Ji a n g N, C a o Y, Al w ali d O, G u J, F a n Y, Z h e n g C. R a di ol o gic al fi n di n gs fr o m 8 1 p ati e nts wit h C O VI D-
1 9 p n e u m o ni a i n W u h a n, C hi n a: a d escri pti v e st u d y. L a nc et I nf ect Dis. 2 0 2 0. E p u b 2 0 2 0/ 0 2/ 2 8. d oi: 1 0. 1 0 1 6/ S 1 4 7 3-
3 0 9 9( 2 0) 3 0 0 8 6- 4. P u b M e d P MI D: 3 2 1 0 5 6 3 7. 
1 2.  
X u Z, S hi L, W a n g Y, Z h a n g J, H u a n g L, Z h a n g C, Li u S, Z h a o P, Li u H, Z h u L, T ai Y, B ai C, G a o T, S o n g J, Xi a P, D o n g 
J, Z h a o J, W a n g F S. P at h ol o gic al fi n di n gs of C O VI D- 1 9 ass oci at e d wit h ac ut e r es pir at or y distr ess s y n dr o m e. L a nc et R es pir 
M e d. 2 0 2 0. E p u b 2 0 2 0/ 0 2/ 2 3. d oi: 1 0. 1 0 1 6/ S 2 2 1 3- 2 6 0 0( 2 0) 3 0 0 7 6- X. P u b M e d P MI D: 3 2 0 8 5 8 4 6. 
1 3.  
Ti a n S, H u W, Ni u L, Li u H, X u H, Xi a o S Y. P ul m o n ar y p at h ol o g y of e arl y p h as e 2 0 1 9 n o v el c or o n a vir us ( C O VI D- 1 9) 
p n e u m o ni a i n t w o p ati e nts wit h l u n g c a nc er. J T h or ac  O nc ol. 2 0 2 0. E p u b 2 0 2 0/ 0 3/ 0 3. d oi: 1 0. 1 0 1 6/j.jt h o. 2 0 2 0. 0 2. 0 1 0. 
P u b M e d P MI D: 3 2 1 1 4 0 9 4. 
1 4.  
C a pl a n AI, C orr e a D. T h e M S C: a n i nj ur y dr u gst o r e. C ell St e m C ell. 2 0 1 1; 9( 1): 1 1- 5. E p u b 2 0 1 1/ 0 7/ 0 6. d oi: 
1 0. 1 0 1 6/j.st e m. 2 0 1 1. 0 6. 0 0 8. P u b M e d P MI D: 2 1 7 2 6 8 2 9; P M CI D: P M C 3 1 4 4 5 0 0. 
1 5.  
G e W, Ji a n g J, Ar p J, Li u W, G arci a B, W a n g H. R e g ul at or y T-c ell g e n er ati o n a n d ki d n e y all o gr aft t ol er a nc e 
i n d uc e d b y m es e nc h y m al st e m c ells ass oci at e d wit h i n d ol e a mi n e 2, 3- di ox y g e n as e ex pr essi o n. Tr a ns pl a nt ati o n. 
2 0 1 0; 9 0( 1 2): 1 3 1 2- 2 0. d oi: 1 0. 1 0 9 7/ T P. 0 b 0 1 3 e 3 1 8 1f e d 0 0 1. P u b M e d P MI D: 2 1 0 4 2 2 3 8. 

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C o nfi de ntial
  
1 6.  
B art h ol o m e w A, St ur g e o n C, Si ats k as M, F err er K, McI n t os h K, P atil S, H ar d y W, D e vi n e S, Uc k er D, D e a ns R, 
M os el e y A, H off m a n R. M es e nc h y m al st e m c ells s u p pr ess l y m p h oc yt e pr olif er ati o n i n vitr o a n d pr ol o n g s ki n gr aft 
s ur vi v al i n vi v o. Ex p H e m at ol. 2 0 0 2; 3 0( 1): 4 2- 8. E p u b 2 0 0 2/ 0 2/ 0 2. P u b M e d P MI D: 1 1 8 2 3 0 3 6. 
1 7.  
C asir a g hi F, Azz olli ni N, C assis P, I m b erti B, M ori gi M, C u gi ni D, C a vi n at o R A, T o d esc hi ni M, S oli ni S, S o nz o g ni A, 
P eric o N, R e m uzzi G, N oris M. Pr etr a ns pl a nt i nf usi o n of m es e nc h y m al st e m c ells pr ol o n gs t h e s ur vi v al of a 
s e mi all o g e n eic h e art tr a ns pl a nt t hr o ug h t h e g e n er ati o n of r e g ul at or y T c ells . J I m m u n ol. 2 0 0 8; 1 8 1( 6): 3 9 3 3- 4 6. E p u b 
2 0 0 8/ 0 9/ 0 5. P u b M e d P MI D: 1 8 7 6 8 8 4 8. 
1 8.  
G e W, Ji a n g J, B ar oj a ML, Ar p J, Z ass o k o R, Li u W, B art h ol o m e w A, G arci a B, W a n g H. I nf usi o n of m es e nc h y m al 
st e m c ells a n d r a p a m yci n s y n er giz e t o att e n u at e all oi m m u n e r es p o ns es a n d pr o m ot e c ar di ac all o gr aft t ol er a nc e. A m J 
Tr a ns pl a nt. 2 0 0 9; 9( 8): 1 7 6 0- 7 2. E p u b 2 0 0 9/ 0 7/ 0 1. d oi: 1 0. 1 1 1 1/j. 1 6 0 0- 6 1 4 3. 2 0 0 9. 0 2 7 2 1.x. P u b M e d P MI D: 1 9 5 6 3 3 4 4. 
1 9.  
Ucc elli A, L ar o ni A, Fr e e d m a n M S. M es e nc h y m al st e m c ells f or t h e tr e at m e nt of m ulti pl e scl er osis a n d ot h er 
n e ur ol o gic al dis e as es. L a nc et N e ur ol. 2 0 1 1; 1 0( 7) : 6 4 9- 5 6. E p u b 2 0 1 1/ 0 6/ 2 1. d oi: 1 0. 1 0 1 6/ S 1 4 7 4- 4 4 2 2( 1 1) 7 0 1 2 1- 1. 
P u b M e d P MI D: 2 1 6 8 3 9 3 0. 
2 0.  
G e W, Ji a n g J, B ar oj a ML, Ar p J, Z ass o k o R, Li u W, B art h ol o m e w A, G arci a B, W a n g H. I nf usi o n of m es e nc h y m al 
st e m c ells a n d r a p a m yci n s y n er giz e t o att e n u at e all oi m m u n e r es p o ns es a n d pr o m ot e c ar di ac all o gr aft t ol er a nc e. A m J 
Tr a ns pl a nt. 2 0 0 9; 9( 8): 1 7 6 0- 7 2. d oi: 1 0. 1 1 1 1/j. 1 6 0 0- 6 1 4 3. 2 0 0 9. 0 2 7 2 1.x. P u b M e d P MI D: 1 9 5 6 3 3 4 4. 
2 1.  
P er ez- Si m o n J A, L o p ez- Vill ar O, A n dr e u EJ, Rif o n J, M u nti o n S, Di ez C a m p el o M, S a nc h ez- G uij o F M, M arti n ez C, 
V alc arc el D, C a niz o C D. M es e nc h y m al st e m c ells ex p a n d e d i n  vitr o wit h h u m a n s er u m f or t h e tr e at m e nt of ac ut e a n d 
c hr o nic gr aft- v ers us- h ost dis e as e: r es ults of a p h as e I/ II cli nic al tri al. H a e m at ol o gic a. 2 0 1 1; 9 6( 7): 1 0 7 2- 6. d oi: 
1 0. 3 3 2 4/ h a e m at ol. 2 0 1 0. 0 3 8 3 5 6. P u b M e d P MI D: 2 1 3 9 3 3 2 6; P M CI D: P M C 3 1 2 8 2 3 0. 
2 2.  
G arci a- Ol m o D, G arci a- Arr a nz M, H err er os D, P asc u al I, P eir o C, R o dri g u ez- M o nt es J A. A p h as e I cli nic al tri al of 
t h e tr e at m e nt of Cr o h n's fist ul a b y a di p os e m es e nc h y m al ste m c ell tr a ns pl a nt ati o n. Dis C ol o n R ect u m. 2 0 0 5; 4 8( 7): 1 4 1 6-
2 3. d oi: 1 0. 1 0 0 7/s 1 0 3 5 0- 0 0 5- 0 0 5 2- 6. P u b M e d P MI D: 1 5 9 3 3 7 9 5. 
2 3.  
S u n L, A ki y a m a K, Z h a n g H, Y a m az a T, H o u Y, Z h a o S, X u T, L e A, S hi S. M es e nc h y m al st e m c ell tr a ns pl a nt ati o n 
r e v ers es m ulti or g a n d ysf u ncti o n i n s yst e mic l u p us eryt h e m at os us mic e a n d h u m a ns. St e m C ells. 2 0 0 9; 2 7( 6): 1 4 2 1- 3 2. 
d oi: 1 0. 1 0 0 2/st e m. 6 8. P u b M e d P MI D: 1 9 4 8 9 1 0 3; P M CI D: P M C 2 7 0 4 2 5 4. 
2 4.  
D h er e T, C o pl a n d I, G arci a M, C hi a n g K Y, C hi n n a d ur ai R, Pr as a d M, G ali p e a u J, K u g at h as a n S. T h e s af et y of 
a ut ol o g o us a n d m et a b olic all y fit b o n e m arr o w m es e nc h y m al str o m al c ells i n m e dic all y r efr act or y Cr o h n's dis e as e - a 
p h as e 1 tri al wit h t hr e e d os es. Ali m e nt P h ar m ac ol T h er. 2 0 1 6; 4 4( 5): 4 7 1- 8 1. d oi: 1 0. 1 1 1 1/ a pt. 1 3 7 1 7. P u b M e d P MI D: 
2 7 3 8 5 3 7 3. 
2 5.  
C arlss o n P O, Sc h w arcz E, K ors gr e n O, L e Bl a nc K. Pr es er v e d b et a-c ell f u ncti o n i n t y p e 1 di a b et es b y m es e nc h y m al 
str o m al c ells. Di a b et es. 2 0 1 5; 6 4( 2): 5 8 7- 9 2. d oi: 1 0. 2 3 3 7/ d b 1 4- 0 6 5 6. P u b M e d P MI D: 2 5 2 0 4 9 7 4. 
2 6.  
C ai J, W u Z, X u X, Li a o L, C h e n J, H u a n g L, W u W, L u o F, W u C, P u gli es e A, Pil e g gi A, Ric or di C, T a n J. U m bilic al 
C or d M es e nc h y m al Str o m al C ell Wit h A ut ol o g o us B o n e M arr o w C ell Tr a ns pl a nt ati o n i n Est a blis h e d T y p e 1 Di a b et es: A 
Pil ot R a n d o miz e d C o ntr oll e d O p e n-L a b el Cli nic al St u d y t o Ass e ss S af et y a n d I m p act o n I ns ulin S ecr eti o n. Di a b et es C ar e. 
2 0 1 6; 3 9( 1): 1 4 9- 5 7. E p u b 2 0 1 5/ 1 2/ 0 3. d oi: 1 0. 2 3 3 7/ dc 1 5- 0 1 7 1. P u b M e d P MI D: 2 6 6 2 8 4 1 6. 
2 7.  
H u J, Y u X, W a n g Z, W a n g F, W a n g L, G a o H, C h e n Y, Z h a o W, Ji a Z, Y a n S, W a n g Y. L o n g t er m eff ects of t h e 
i m pl a nt ati o n of W h art o n's j ell y- d eri v e d m es e nc h y m al st e m c ells fr o m t h e u m bilic al c or d f or n e wl y- o ns et t y p e 1 di a b et es 
m ellit us. E n d ocr J. 2 0 1 3; 6 0( 3): 3 4 7- 5 7. P u b M e d P MI D: 2 3 1 5 4 5 3 2. 
2 8.  
M or a n d o S, Vi g o T, Es p osit o M, C as a zz a S, N o vi G, Pri nci p at o M C, F url a n R, Ucc elli A. T h e t h er a p e utic eff ect of 
m es e nc h y m al st e m c ell tr a ns pl a nt ati o n i n ex p eri m e nt al a ut o i m m u n e e nc e p h al o m y elitis is m e di at e d b y p eri p h er al a n d 
c e ntr al m ec h a nis ms. St e m C ell R es T h er. 2 0 1 2; 3( 1): 3. E p u b 2 0 1 2/ 0 1/ 2 7. d oi:  1 0. 1 1 8 6/scrt 9 4. P u b M e d P MI D: 2 2 2 7 7 3 7 4. 
2 9.  
H e d a y at p o ur A, R a g er di I, P as b a k hs h P, K af a mi L, Atl asi N, Pir h aj ati M a h a b a di V, G h as e mi S, R ez a M. Pr o m oti o n 
of r e m y eli n ati o n b y a di p os e m es e nc h y m al st e m c ell tr a ns pl a nt ati o n i n a c u priz o n e m o d el of m ulti pl e scl er osis. C ell J. 
2 0 1 3; 1 5( 2): 1 4 2- 5 1. E p u b 2 0 1 3/ 0 7/ 1 9. P u b M e d P MI D: 2 3 8 6 2 1 1 6; P M CI D: 3 7 1 2 7 7 5. 
3 0.  
Al J u m a h M A, A b u m ar e e M H. T h e i m m u n o m o d ul at or y a n d n e ur o pr ot ecti v e eff ects of m es e nc h y m al st e m c ells 
( M S Cs) i n ex p eri m e nt al a ut oi m m u n e e nc e p h al o m y elitis ( E A E): a m o d el of m ulti pl e scl er osis ( M S). I nt J M ol Sci. 
2 0 1 2; 1 3( 7): 9 2 9 8- 3 3 1. d oi: 1 0. 3 3 9 0/ij ms 1 3 0 7 9 2 9 8. P u b M e d P MI D: 2 2 9 4 2 7 6 7; P M CI D: P M C 3 4 3 0 2 9 8. 
3 1.  
B art ol ucci J, V er d u g o FJ, G o nz al ez PL, L arr e a R E, A b arz u a E, G os et C, R oj o P, P al m a I, L a mic h R, P e dr er os P A, 
V al di vi a G, L o p ez V M, N azz al C, Alc a y a g a - Mir a n d a F, C u e nc a J, Br o b ec k MJ, P at el A N, Fi g u er o a F E, K h o ur y M. S af et y a n d 
Effic ac y of t h e I ntr a v e n o us I nf usi o n of U m bilic al C or d M es e nc h y m a l St em  C ells i n P ati e nts Wit h H e art F ail ur e: A P h as e 

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1/ 2 R a n d o miz e d C o ntr oll e d Tri al ( RI M E C A R D Tri al [ R a n d o miz e d Cli nic al Tri al of I ntr a v e n o us I nf usi o n U m bilic al C or d 
M es e nc h y m al St e m C ells o n C ar di o p at h y]). Circ R es. 2 0 1 7; 1 2 1( 1 0): 1 1 9 2- 2 0 4. d oi:  1 0. 1 1 6 1/ CI R C R E S A H A. 1 1 7. 3 1 0 7 1 2. 
P u b M e d P MI D: 2 8 9 7 4 5 5 3. 
3 2.  
T u m a J, C arr asc o A, C astill o J, Cr uz C, C arrill o A, Ercill a J, Y arl e q u e C, C u nz a J, B artl ett C E, Wi nt ers A A, Sil v a FJ, 
P at el A N. R E S C U E- H F Tri al: R etr o gr a d e D eli v er y of All o g e n eic U m bilic al C or d Li ni n g S u b e pit h eli al C ells i n P ati e nts Wit h 
H e art F ail ur e. C ell Tr a ns pl a nt. 2 0 1 6; 2 5( 9): 1 7 1 3- 2 1. d oi: 1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 5 X 6 9 0 3 1 4. P u b M e d P MI D: 2 6 7 6 3 1 9 8. 
3 3.  
Fr a n q u es a M, H o o g d uij n MJ, R ei n d ers M E, E g g e n h of er E,  E n g el a A U, M e ns a h F K, T orr as J, Pil e g gi A, v a n K o ot e n 
C, M a h o n B, D etr y O, P o p p F C, B e ns el er V, C asir a g hi F, J o h ns o n C, A nc a ns J, Fill e n b er g B, d el a R os a O, Ar a n J M, 
R o e m eli n g- v a n R hij n M, Pi nxt er e n J, P eric o N, G otti E, C hrist  B, R e a di n g J, I ntr o n a M, D e a ns R, S h a gi d uli n M, F arr e R, 
R a m b al di A, S a nc h ez- F u e y o A, O b er m aj er N, P uli n A, D or FJ, P ort er o- S a nc h ez I, B a a n C C, R a b eli n k TJ, R e m uzzi G, B etj es 
M G, D a hl k e M H, Gri n y o J M, Mi S O T S G. M es e nc h y m al St e m C ells  i n S oli d Or g a n Tr a ns pl a nt ati o n ( Mi S O T) F o urt h M e eti n g: 
l ess o ns l e ar n e d fr o m first cli nic al tri als. Tr a ns pl a nt ati o n. 2 0 1 3; 9 6( 3): 2 3 4-8. E p u b 2 0 1 3/ 0 6/ 1 4. d oi: 
1 0. 1 0 9 7/ T P. 0 b 0 1 3 e 3 1 8 2 9 8f 9f a. P u b M e d P MI D: 2 3 7 5 9 8 7 9; P M CI D: P M C 3 7 3 7 3 9 2. 
3 4.  
M or o nci ni G, P a oli ni C, Orl a n d o F, C a p elli C, Gri ec o A, T o n ni ni C, A g ar b ati S, M o n di ni E, S acc o m a n n o S, G ot eri G, 
S v e gli ati B ar o ni S, Pr o vi nci ali M, I ntr o n a M, D el P a p a N, G a bri elli A. M es e nc h y m al str o m al c ells fr o m h u m a n u m bilic al 
c or d pr e v e nt t h e d e v el o p m e nt of l u n g fi br osis i n i m m u n oc o m p et e nt mic e. PL o S O n e. 2 0 1 8; 1 3( 6): e 0 1 9 6 0 4 8. E p u b 
2 0 1 8/ 0 6/ 0 2. d oi: 1 0. 1 3 7 1/j o ur n al. p o n e. 0 1 9 6 0 4 8. P u b M e d P MI D: 2 9 8 5 6 7 3 7; P M CI D: P M C 5 9 8 3 5 0 6. 
3 5.  
Z h a n g C, Yi n X, Z h a n g J, A o Q, G u Y, Li u Y. Cli nic al o bs er v ati o n of u m bilic al c or d m es e nc h y m al st e m c ell 
tr e at m e nt of s e v er e i di o p at hic p ul m o n ar y fi br osis: A c as e r e p ort. Ex p T h er M e d. 2 0 1 7; 1 3( 5): 1 9 2 2- 6. E p u b 2 0 1 7/ 0 6/ 0 2. 
d oi: 1 0. 3 8 9 2/ et m. 2 0 1 7. 4 2 2 2. P u b M e d P MI D: 2 8 5 6 5 7 8 7; P M CI D: P M C 5 4 4 3 2 9 9. 
3 6.  
M o o dl e y Y, V a g hji a ni V, C h a n J, B altic S, R y a n M, Tc h o n g u e J, S a m u el C S, M urt hi P, P ar oli ni O, M a n u el pill ai U. 
A nti-i nfl a m m at or y eff ects of a d ult st e m c ells i n s ust ai n e d l u n g i nj ur y: a c o m p ar ati v e st u dy. PL o S O n e. 2 0 1 3; 8( 8): e 6 9 2 9 9. 
E p u b 2 0 1 3/ 0 8/ 1 3. d oi: 1 0. 1 3 7 1/j o ur n al. p o n e. 0 0 6 9 2 9 9.  P u b M e d P MI D: 2 3 9 3 6 3 2 2; P M CI D: P M C 3 7 3 1 3 0 5. 
3 7.  
H arr ell C R, S a di k ot R, P asc u al J, F ell a b a u m C, J a n k o vic  M G, J o vicic N, Dj o n o v V, Ars e nij e vic N, V ol ar e vic V. 
M es e nc h y m al St e m C ell- B as e d T h er a p y of I nfl a m m at or y L u n g Dis e as es: C urr e nt U n d erst a n di n g a n d F ut ur e P ers p ecti v es. 
St e m C ells I nt. 2 0 1 9; 2 0 1 9: 4 2 3 6 9 7 3. E p u b 2 0 1 9/ 0 6/ 1 4. d oi:  1 0. 1 1 5 5/ 2 0 1 9/ 4 2 3 6 9 7 3. P u b M e d P MI D: 3 1 1 9 1 6 7 2; P M CI D: 
P M C 6 5 2 5 7 9 4. 
3 8.  
L e n g Z, Z h u R, H o u W, F e n g Y, Y a n g Y, H a n Q, S h a n G, M e n g F, D u D, W a n g S, F a n J, W a n g W, D e n g L, S hi H, Li H, 
H u Z, Z h a n g F, G a o J, Li u H, Li X, Z h a o Y, Yi n K, H e X, G a o Z,  W a n g Y, Y a n g B, Ji n R, St a m bl er I, W ei Li m L, S u H, M os k al e v 
A, C a n o A, C h a kr a b arti S, Mi n K-J, Ellis o n- H u g h es G, C ar us o  C, Ji n K, Z h a o R C. Tr a ns pl a nt ati o n of A C E 2- m es e nc h y m al 
st e m c ells i m pr o v es t h e o utc o m e of p ati e nts wit h C O VI D- 1 9 p n e u m o ni a. C hi n a Xi v. 2 0 2 0. d oi: 1 0. 1 2 0 7 4/ 2 0 2 0 0 2. 0 0 0 8 0. 
3 9.  
Li a n g B, C h e n J, Li T, W u H, Y a n g W, Li Y, Li J, Y u C,  Ni e F, M a Z, Y a n g M, Ni e P, G a o Y, Qi a n C, H u M. Cli nic al 
r e missi o n of a critic all y ill C O VI D- 1 9 p ati e nt tr e at e d b y h u m a n u m bilic al c or d m es e nc h y m al st e m c ells. C hi n a Xi v. 2 0 2 0. 
d oi: 1 0. 1 2 0 7 4/ 2 0 2 0 0 2. 0 0 0 8 4. 
4 0.  
Zi k u a n L e n g R Z, W ei H o u, Yi n g m ei F e n g, Y a nl ei Y a n g,  Qi n H a n, G u a n gli a n g S h a n, F a n y a n M e n g, D o n gs h u D u, 
S hi h u a W a n g, J u nf e n F a n, W e nji n g W a n g, L uc h a n D e n g, H o n g b o  S hi, H o n gj u n Li, Z h o n gji e H u, F e n gc h u n Z h a n g, Ji n mi n g 
G a o, H o n gji a n Li u, Xi a oxi a Li, Y a n g y a n g Z h a o, K a n Yi n, Xiji n g H e, Z h e n gc h a o G a o, Yi bi n W a n g, B o Y a n g, R o n g h u a Ji n, Ili a 
St a m bl er, L e e W ei Li m, H u a nxi n g S u, Al ex e y M os k al e v, A n t o ni o C a n o, S as a n k a C h a kr a b arti, K y u n g-Ji n Mi n, G e or gi n a 
Ellis o n- H u g h es, C al o g er o C ar us o, K u nli n Ji n, R o b ert C h u n h u a Z h a o. Tr a ns pl a nt ati o n of A C E 2 <s u p >- </s u p > M es e nc h y m al 
St e m C ells I m pr o v es t h e O utc o m e of P ati e nts wit h C O VI D- 1 9 P n e u m o ni a. A g i n g a n d dis e as e. 2 0 2 0; 1 1( 2): 2 1 6- 2 8. d oi: 
1 0. 1 4 3 3 6/ a d. 2 0 2 0. 0 2 2 8. 
4 1.  
P e n g Z. U m bilic al C or d( U C)- D eri v e d M es e nc h y m al St e m C ells( M S Cs) Tr e at m e nt f or t h e 2 0 1 9- n o v el 
C or o n a vir us( n C O V) P n e u m o ni a. 
4 2.  
P at el A N V V, R a v el o o P, B ull D A. M es e nc h y m al St e m C e ll P o p ul ati o n Is o alt e d Fr o m t h e S u b e pit h eli al L a y er of 
U m bilic al C or d Tiss u e. C ell Tr a ns pl a nt ati o n. 2 0 1 3: 5 1 3- 9. 
4 3.  
B a u m el B. A P h as e I, Pr os p ecti v e, O p e n-l a b el Tri al t o  E v al u at e t h e S af et y, T ol er a bilit y a n d Ex pl or at or y O utc o m es 
of M ulti pl e All o g e n eic H u m a n M es e nc h y m a l St e m C ells ( H M S C) I nf usi o ns i n P ati e nts Wit h Mil d t o M o d er at e Alz h ei m er's 
Dis e as e  [cit e d 2 0 2 0 M arc h 9]. 
4 4.  
C h a n n a p p a n a v ar R, P erl m a n S. P at h o g e nic h u m a n c or o n a vir us i nf ecti o ns: c a us es a n d c o ns e q u e nc es of c yt o ki n e 
st or m a n d i m m u n o p at h ol o g y. S e mi n I m m u n o p at h ol. 2 0 1 7; 3 9( 5): 5 2 9- 3 9. E p u b 2 0 1 7/ 0 5/ 0 4. d oi: 1 0. 1 0 0 7/s 0 0 2 8 1- 0 1 7-
0 6 2 9-x. P u b M e d P MI D: 2 8 4 6 6 0 9 6. 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
5 4 | P a g e  
 
 
C o nfi de ntial
  
4 5.  
Al g a ht a ni H, S u b a hi A, S hir a h B. N e ur ol o gic al C o m pli c ati o ns of Mi d dl e E ast R es pir at or y S y n dr o m e C or o n a vir us: A 
R e p ort of T w o C as es a n d R e vi e w of t h e Lit er at ur e. C as e R e p N e ur ol M e d. 2 0 1 6; 2 0 1 6: 3 5 0 2 6 8 3. E p u b 2 0 1 6/ 0 5/ 3 1. d oi: 
1 0. 1 1 5 5/ 2 0 1 6/ 3 5 0 2 6 8 3. P u b M e d P MI D: 2 7 2 3 9 3 5 6; P M CI D: P M C 4 8 6 4 5 6 0. 
4 6.  
H a wi g er J, V e ac h R A, Zi e n ki e wicz J. N e w p ar a di g ms i n s e psis: fr o m pr e v e nti o n t o pr ot ecti o n of f aili n g 
micr ocirc ul ati o n. J T hr o m b H a e m ost. 2 0 1 5; 1 3( 1 0): 1 7 4 3- 5 6. E p u b 2 0 1 5/ 0 7/ 2 1. d oi: 1 0. 1 1 1 1/jt h. 1 3 0 6 1. P u b M e d P MI D: 
2 6 1 9 0 5 2 1; P M CI D: P M C 5 0 1 4 1 4 9. 
4 7.  
M att h a y M A, W ar e L B, Zi m m er m a n G A. T h e ac ut e r es pir at or y distr ess s y n dr o m e. J Cli n I n v est. 
2 0 1 2; 1 2 2( 8): 2 7 3 1- 4 0. E p u b 2 0 1 2/ 0 8/ 0 2. d oi: 1 0. 1 1 7 2/J CI 6 0 3 3 1. P u b M e d P MI D: 2 2 8 5 0 8 8 3; P M CI D: P M C 3 4 0 8 7 3 5. 
4 8.  
N a nc h al R S, Tr u wit J D. R ec e nt a d v a nc es i n u n d erst a n di n g a n d tr e ati n g ac ut e r es pir at or y distr ess s y n dr o m e. 
F 1 0 0 0 R es. 2 0 1 8; 7. E p u b 2 0 1 8/ 0 9/ 1 4. d oi: 1 0. 1 2 6 8 8/f 1 0 0 0r es e arc h. 1 5 4 9 3. 1. P u b M e d P MI D: 3 0 2 1 0 7 8 1; P M CI D: 
P M C 6 1 0 7 9 8 3. 
4 9.  
B ell a ni G, L aff e y J G, P h a m T, F a n E,  Br oc h ar d L, Est e b a n A, G atti n o ni L, v a n H ar e n F, L arss o n A, Mc A ul e y D F, 
R a ni eri M, R u b e nf el d G, T h o m ps o n B T, Wri g g e H, Sl uts k y A S, P es e nti A, I n v esti g at ors L S, Gr o u p E T. E pi d e mi ol o g y, 
P att er ns of C ar e, a n d M ort alit y f or P ati e nts Wit h Ac ut e R es pir at or y Distr ess S y n dr o m e i n I nt e nsi v e C ar e U nits i n 5 0 
C o u ntri es. J A M A. 2 0 1 6; 3 1 5( 8): 7 8 8- 8 0 0. E p u b 2 0 1 6/ 0 2/ 2 4.  d oi: 1 0. 1 0 0 1/j a m a. 2 0 1 6. 0 2 9 1. P u b M e d P MI D: 2 6 9 0 3 3 3 7. 
5 0.  
Wils o n J G, Li u K D, Z h u o H, C a b all er o L, Mc Mill a n M, F a n g X, C os gr o v e K, V oj ni k R, C alf e e C S, L e e J W, R o g ers AJ, 
L e vitt J, Wi e n er- Kr o nis h J, B aj w a E K, L e a vitt A, Mc K e n n a D, T h o m ps o n B T, M att h a y M A. M es e nc h y m al st e m (str o m al) 
c ells f or tr e at m e nt of A R D S: a p h as e 1 cli nic al tri al. L a nc et R es pir M e d. 2 0 1 5; 3( 1): 2 4- 3 2. E p u b 2 0 1 4/ 1 2/ 2 3. d oi: 
1 0. 1 0 1 6/ S 2 2 1 3- 2 6 0 0( 1 4) 7 0 2 9 1- 7. P u b M e d P MI D: 2 5 5 2 9 3 3 9; P M CI D: P M C 4 2 9 7 5 7 9. 
5 1.  
M att h a y M A, C alf e e C S, Z h u o H, T h o m ps o n B T, Wils o n J G, L e vitt J E, R o g ers AJ, G otts J E, Wi e n er- Kr o nis h J P, 
B aj w a E K, D o n a h o e M P, Mc V err y BJ, Ortiz L A, Exli n e M, C hrist m a n J W, A b b ott J, D el ucc hi KL, C a b all er o L, Mc Mill a n M, 
Mc K e n n a D H, Li u K D. Tr e at m e nt wit h all o g e n eic m es e nc h y m al str o m al c ells f or m o d er at e t o s e v er e ac ut e r es pir at or y 
distr ess s y n dr o m e ( S T A R T st u d y): a r a n d o mis e d p h as e 2 a s a f et y tri al. L a nc et R es pir M e d. 2 0 1 9; 7( 2): 1 5 4- 6 2. E p u b 
2 0 1 8/ 1 1/ 2 1. d oi: 1 0. 1 0 1 6/ S 2 2 1 3- 2 6 0 0( 1 8) 3 0 4 1 8- 1. P u b M e d P MI D: 3 0 4 5 5 0 7 7. 
5 2.  
Z h a o R, S u Z, W u J, Ji HL. S eri o us a d v ers e e v e nts of c ell t h er a p y f or r es pir at or y dis eas es: a s yst e m atic r e vi e w a n d 
m et a- a n al ysis. O nc ot ar g et. 2 0 1 7; 8( 1 8): 3 0 5 1 1- 2 3. E p u b 2 0 1 7/ 0 4/ 2 2. d oi: 1 0. 1 8 6 3 2/ o nc ot ar g et. 1 5 4 2 6. P u b M e d P MI D: 
2 8 4 3 0 6 2 2; P M CI D: P M C 5 4 4 4 7 6 1. 
5 3.  
L aff e y J G, M att h a y M A. Fift y Y e ars of R es e arc h i n A R D S. C ell- b as e d T h er a p y f or Ac ut e R es pir at or y Distr ess 
S y n dr o m e. Bi ol o g y a n d P ot e nti al T h er a p e utic V al u e. A m J R es pir Crit C ar e  M e d. 2 0 1 7; 1 9 6( 3): 2 6 6- 7 3. E p u b 2 0 1 7/ 0 3/ 1 8. 
d oi: 1 0. 1 1 6 4/rcc m. 2 0 1 7 0 1- 0 1 0 7 C P. P u b M e d  P MI D: 2 8 3 0 6 3 3 6; P M CI D: P M C 5 5 4 9 8 6 8. 
5 4.  
v o n B a hr V, Mill ar J E, M alf ert h ei n er M V, Ki K K, P ass m or e M R, B art ni k o ws ki N, R e d d M A, C a v a y e M, S u e n J Y, 
Mc A ul e y D F, Fr as er J F. M es e nc h y m al st e m c ells m a y a m eli or at e  i nfl a m m ati o n i n a n ex vi v o m o d el of extr ac or p or e al 
m e m br a n e ox y g e n ati o n. P erf usi o n. 2 0 1 9; 3 4( 1 _s u p pl): 1 5- 2 1. E p u b 2 0 1 9/ 0 4/ 1 1. d oi: 1 0. 1 1 7 7/ 0 2 6 7 6 5 9 1 1 9 8 3 0 8 5 7. 
P u b M e d P MI D: 3 0 9 6 6 9 0 7. 
5 5.  
H u p p ert L A, Li u K D, M att h a y M A. T h er a p e utic p ot e nti al of m es e nc h y m al str o m al c ells i n t h e tr e at m e nt of A R D S. 
Tr a nsf usi o n. 2 0 1 9; 5 9( S 1): 8 6 9- 7 5. E p u b 2 0 1 8/ 1 1/ 0 2.  d oi: 1 0. 1 1 1 1/trf. 1 4 8 3 5. P u b M e d P MI D: 3 0 3 8 3 2 9 0. 
5 6.  
J u n g YJ, P ar k Y Y, H u h J W, H o n g S B. T h e eff ect of h u m a n a di p os e- d eri v e d st e m c ells o n li p o p ol ys acc h ari d e-
i n d uc e d ac ut e r es pir at or y distr ess s y n dr o m e i n mic e. A n n Tr a nsl M e d. 2 0 1 9; 7( 2 2): 6 7 4. E p u b 2 0 2 0/ 0 1/ 1 4. d oi: 
1 0. 2 1 0 3 7/ at m. 2 0 1 9. 1 0. 4 8. P u b M e d P M I D: 3 1 9 3 0 0 7 5; P M CI D: P M C 6 9 4 4 6 0 0. 
5 7.  
C h e n C H, C h e n YL, S u n g P H, S u n C K, C h e n K H, C h e n YL, H u a n g T H, L u HI, L e e F Y, S h e u JJ, C h u n g S Y, L e e M S, Yi p 
H K. Eff ecti v e pr ot ecti o n a g ai nst ac ut e r es pir at or y distr ess s y n dr o m e/s e psis i nj ur y b y c o m bi n e d a di p os e- d eri v e d 
m es e nc h y m al st e m c ells a n d pr e acti v at e d dis a g gr e g at e d pl at el ets. O nc o t ar g et. 2 0 1 7; 8( 4 7): 8 2 4 1 5- 2 9. E p u b 2 0 1 7/ 1 1/ 1 6. 
d oi: 1 0. 1 8 6 3 2/ o nc ot ar g et. 1 9 3 1 2. P u b M e d  P MI D: 2 9 1 3 7 2 7 4; P M CI D: P M C 5 6 6 9 9 0 0. 
5 8.  
L u H, C o o k T, P oiri er C, M erf el d- Cl a uss S, P etr ac h e I, M arc h KL, B o g atc h e v a N V. P ul m o n ar y R et e nti o n of A di p os e 
Str o m al C ells F oll o wi n g I ntr a v e n o us D eli v er y Is M ar k e dl y Alt er e d i n t h e Pr es e nc e of A R D S. C ell Tr a ns pl a nt. 
2 0 1 6; 2 5( 9): 1 6 3 5- 4 3. E p u b 2 0 1 5/ 1 1/ 2 7. d oi:  1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 5 X 6 9 0 1 8 9. P u b M e d P MI D: 2 6 6 0 9 6 9 3. 
5 9.  
Z h e n g G, H u a n g L, T o n g H, S h u Q, H u Y, G e M, D e n g K, Z h a n g L, Z o u B, C h e n g B, X u J. Tr e at m e nt of ac ut e 
r es pir at or y distr ess s y n dr o m e wit h all o g e n eic a di p os e-d eri v e d m es e nc h y m al st e m c ells: a r a n d o miz e d, pl ac e b o-
c o ntr oll e d pil ot st u d y. R es pir R es. 2 0 1 4; 1 5: 3 9. E p u b 2 0 1 4/ 0 4/ 0 9. d oi: 1 0. 1 1 8 6/ 1 4 6 5- 9 9 2 1- 1 5- 3 9. P u b M e d P MI D: 
2 4 7 0 8 4 7 2; P M CI D: P M C 3 9 9 4 2 0 4. 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
5 5 | P a g e  
 
 
C o nfi de ntial
  
6 0.  
L u Z, C h a n g W, M e n g S, X u X, Xi e J, G u o F, Y a n g Y, Qi u H, Li u L. M es e nc h y m al st e m c ells i n d uc e d e n dritic c ell 
i m m u n e t ol er a nc e vi a p ar acri n e h e p at oc yt e gr o wt h f act or t o all e vi at e ac ut e l u n g i nj ur y. St e m C ell R es T h er. 
2 0 1 9; 1 0( 1): 3 7 2. E p u b 2 0 1 9/ 1 2/ 0 6. d oi: 1 0. 1 1 8 6/s 1 3 2 8 7- 0 1 9- 1 4 8 8- 2. P u b M e d P MI D: 3 1 8 0 1 6 2 6; P M CI D: P M C 6 8 9 4 2 2 6. 
6 1.  
Sil v a J D, d e C astr o LL, Br a g a CL, Oli v eir a G P, Tri v eli n S A, B ar b os a-J u ni or C M, M or a l es M M, D os S a nt os C C, W eiss 
DJ, L o p es- P ac h ec o M, Cr uz F F, R occ o P R M. M es e nc h y m al Str o m al C ells Ar e M or e  Eff ecti v e T h a n T h eir Extr ac ell ul ar 
V esicl es at R e d uci n g L u n g I nj ur y R e g ar dl ess of Ac ut e R es pir at or y Distr ess S y n dr o m e Eti ol o g y. St e m C ells I nt. 
2 0 1 9; 2 0 1 9: 8 2 6 2 8 4 9. E p u b 2 0 1 9/ 0 9/ 1 9. d oi: 1 0. 1 1 5 5/ 2 0 1 9/ 8 2 6 2 8 4 9. P u b M e d P MI D: 3 1 5 3 1 0 2 6; P M CI D: P M C 6 7 2 0 7 2 2 
p u blic ati o n of t his m a n uscri pt. 
6 2.  
X u AL, R o dri g u ez L A, 2 n d, W al k er K P, 3r d, M o h a m m a di p o or A, K a m uc h e k a R M, C a nci o L C, B atc hi ns k y AI, A nt e bi 
B. M es e nc h y m al St e m C ells R ec o n diti o n e d i n T h eir O w n S er u m Ex hi bit A u g m e nt e d T h er a p e utic Pr o p erti es i n t h e S etti n g 
of Ac ut e R es pir at or y Distr ess S y n dr o m e. St e m C ells Tr a nsl M e d. 2 0 1 9; 8( 1 0): 1 0 9 2- 1 0 6. E p u b 2 0 1 9/ 0 6/ 2 1. d oi: 
1 0. 1 0 0 2/sct m. 1 8- 0 2 3 6. P u b M e d P M I D: 3 1 2 1 9 2 4 7; P M CI D: P M C 6 7 6 6 6 9 0. 
6 3.  
C ar d e n es N, Ar a n d a- V al d err a m a P, C ar n e y J P, S ell ar es T orr es J, Al v ar ez D,  K oc y diri m E, W olfr a m S mit h J A, Ti n g 
A E, L a g azzi L, Y u Z, M as o n S, S a nt os E, L o pr esti BJ, R oj as M. C ell t h er a p y f or A R D S: effic ac y of e n d o br o nc hi al v ers us 
i ntr a v e n o us a d mi nistr ati o n a n d bi o distri b uti o n of M A PCs i n a l ar g e a ni m al m o d el. B MJ O p e n R es pir R es. 
2 0 1 9; 6( 1): e 0 0 0 3 0 8. E p u b 2 0 1 9/ 0 2/ 0 5. d oi: 1 0. 1 1 3 6/ b m jr es p- 2 0 1 8- 0 0 0 3 0 8. P u b M e d P MI D: 3 0 7 1 3 7 1 3; P M CI D: 
P M C 6 3 3 9 9 9 2. 
6 4.  
Li L, D o n g L, Z h a n g J, G a o F, H ui J, Y a n J. M es e nc h y m al st e m c ells wit h d o w nr e g ul at e d Hi p p o si g n ali n g att e n u at e 
l u n g i nj ur y i n mic e wit h li p o p ol ys acc h ari d ei n d uc e d ac ut e r es pir at or y distr ess s y n dr o m e. I nt J M ol M e d. 2 0 1 9; 4 3( 3): 1 2 4 1-
5 2. E p u b 2 0 1 9/ 0 1/ 1 1. d oi: 1 0. 3 8 9 2/ij m m. 2 0 1 8. 4 0 4 7.  P u b M e d P MI D: 3 0 6 2 8 6 5 2; P M CI D: P M C 6 3 6 5 0 7 4. 
6 5.  
M o k h b er D ezf o uli M R, J a b b ari F a k hr M, S a d e g hi a n C h al es ht ori S, D e h g h a n M M, V aj hi A, M o k ht ari R. 
I ntr a p ul m o n ar y a ut ol o g o us tr a ns pl a nt of b o n e m arr o w- d eri v e d m es e nc h y m al str o m al c ells i m pr o v es li p o p ol ys acc h ari d e-
i n d uc e d ac ut e r es pir at or y distr ess s y n dr o m e i n r a b bit. Crit C ar e. 2 0 1 8; 2 2( 1): 3 5 3. E p u b 2 0 1 8/ 1 2/ 2 4. d oi: 
1 0. 1 1 8 6/s 1 3 0 5 4- 0 1 8- 2 2 7 2-x. P u b M e d P MI D: 3 0 5 7 2 9 1 3; P M CI D: P M C 6 3 0 2 4 0 8. 
6 6.  
Sc h w e d e M, Wilf o n g E M, Z e m a ns RL, L e e PJ, D os S a nt os C, F a n g X, M att h a y M A. Eff ects of b o n e m arr o w- d eri v e d 
m es e nc h y m al str o m al c ells o n g e n e ex pr essi o n i n h u m a n al v e ol ar t y p e II c ells ex p os e d t o T N F- al p h a, IL- 1 b et a, a n d I F N-
g a m m a. P h ysi ol R e p. 2 0 1 8; 6( 1 6): e 1 3 8 3 1. E p u b 2 0 1 8/ 0 8/ 2 4.  d oi: 1 0. 1 4 8 1 4/ p h y 2. 1 3 8 3 1. P u b M e d P MI D: 3 0 1 3 6 4 1 0; 
P M CI D: P M C 6 1 0 5 6 2 7. 
6 7.  
M ast ers o n C, D e v a n e y J, H ori e S, O' Fl y n n L, D e e di g a n L, Elli m a n S, B arr y F, O' Bri e n T, O' T o ol e D, L aff e y J G. 
S y n d ec a n- 2- p ositi v e, B o n e M arr o w- d eri v e d H u m a n M es e nc h y m a l Str o m al C ells Att e n u at e B act eri al-i n d uc e d Ac ut e L u n g 
I nj ur y a n d E n h a nc e R es ol uti o n of V e ntil at or-i n d uc e d Lu n g I nj ur y i n R ats. A n est h es i ol o g y. 2 0 1 8; 1 2 9( 3): 5 0 2- 1 6. E p u b 
2 0 1 8/ 0 7/ 0 7. d oi: 1 0. 1 0 9 7/ AL N. 0 0 0 0 0 0 0 0 0 0 0 0 2 3 2 7. P u b M e d P MI D: 2 9 9 7 9 1 9 1. 
6 8.  
P ar k J, J e o n g S, P ar k K, Y a n g K, S hi n S. Ex pr essi o n pr ofil e of micr o R N As f oll o wi n g b o n e m arr o w- d eri v e d 
m es e nc h y m al st e m c ell tr e at m e nt i n li p o p ol ys acc h ari d e-i n d uc e d ac ut e l u n g i nj ur y. Ex p T h er M e d. 2 0 1 8; 1 5( 6): 5 4 9 5- 5 0 2. 
E p u b 2 0 1 8/ 0 6/ 1 6. d oi: 1 0. 3 8 9 2/ et m. 2 0 1 8. 6 1 1 8. P u b M e d P MI D: 2 9 9 0 4 4 3 0;  P M CI D: P M C 5 9 9 6 6 6 5. 
6 9.  
P e dr azz a L, C u n h a A A, L uft C, N u n es N K, Sc hi mitz F, G ass e n R B, Br e d a R V, D o n a di o M V, d e S o uz a W ys e A T, Pitr ez 
P M C, R os a JL, d e Oli v eir a J R. M es e nc h y m al st e m c ells i m pr o v es  s ur vi v al i n L P S-i n d uc e d ac ut e l u n g i nj ur y acti n g t hr o u g h 
i n hi biti o n of N E Ts f or m ati o n. J C ell P h ysi ol. 2 0 1 7; 2 3 2(1 2): 3 5 5 2- 6 4. E p u b 2 0 1 7/ 0 1/ 2 4. d oi: 1 0. 1 0 0 2/jc p. 2 5 8 1 6. P u b M e d 
P MI D: 2 8 1 1 2 3 9 1. 
7 0.  
Y a n g Y, H u S, X u X, Li J, Li u A, H a n J, Li u S, Li u L,  Qi u H. T h e V asc ul ar E n d ot h eli al Gr o wt h F act ors- Ex pr essi n g 
C h ar act er of M es e nc h y m al St e m C ells Pl a ys a P ositi v e R ol e i n Tr e at m e nt of Ac ut e L u n g I nj ur y I n Vi v o. M e di at ors 
I nfl a m m. 2 0 1 6; 2 0 1 6: 2 3 4 7 9 3 8. E p u b 2 0 1 6/ 0 6/ 1 8. d oi: 1 0. 1 1 5 5/ 2 0 1 6/ 2 3 4 7 9 3 8. P u b M e d P MI D: 2 7 3 1 3 3 9 8; P M CI D: 
P M C 4 8 9 5 0 4 7. 
7 1.  
M o o dl e y Y, St ur m M, S h a w K, S hi m b ori C, T a n D B, K o l b M, Gr a h a m R. H u m a n m es e nc h y m al st e m c ells att e n u at e 
e arl y d a m a g e i n a v e ntil at e d pi g m o d el of ac ut e l u n g i nj ur y. St e m C ell R e s. 2 0 1 6; 1 7( 1): 2 5- 3 1. E p u b 2 0 1 6/ 0 5/ 2 8. d oi: 
1 0. 1 0 1 6/j.scr. 2 0 1 6. 0 5. 0 0 5. P u b M e d P MI D: 2 7 2 3 1 9 8 5. 
7 2.  
H a y es M, C url e y G F, M ast ers o n C, D e v a n e y J, O' T o ol e D, L aff e y J G. M es e nc h y m al str o m al c ells ar e m or e eff ecti v e 
t h a n t h e M S C s ecr et o m e i n di mi nis hi n g i nj ur y a n d e n h a nci n g r ec o v er y f oll o wi n g v e ntil at or-in d uc e d l u n g i nj ur y. I nt e nsi v e 
C ar e M e d Ex p. 2 0 1 5; 3( 1): 2 9. E p u b 2 0 1 5/ 1 0/ 1 7. d oi: 1 0. 1 1 8 6/s 4 0 6 3 5- 0 1 5- 0 0 6 5- y. P u b M e d P MI D: 2 6 4 7 2 3 3 4; P M CI D: 
P M C 4 6 0 7 6 8 5. 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
5 6 | P a g e  
 
 
C o nfi de ntial
  
7 3.  
M o ns el A, Z h u Y G, G e n n ai S, H a o Q, H u S, R o u b y JJ, R os e nz w aj g M, M att h a y M A, L e e J W. T h er a p e utic Eff ects of 
H u m a n M es e nc h y m al St e m C ell- d eri v e d Micr o v esicl es i n S e v e r e P n e u m o ni a i n Mic e. A m J R es pir Crit C ar e M e d. 
2 0 1 5; 1 9 2( 3): 3 2 4- 3 6. E p u b 2 0 1 5/ 0 6/ 1 3. d oi: 1 0. 1 1 6 4/r cc m. 2 0 1 4 1 0- 1 7 6 5 O C. P u b M e d P MI D: 2 6 0 6 7 5 9 2; P M CI D: 
P M C 4 5 8 4 2 5 1. 
7 4.  
H a o Q, Z h u Y G, M o ns el A, G e n n ai S, L e e T, X u F, L e e J W. St u d y of B o n e M arr o w a n d E m br y o nic St e m C ell- D eri v e d 
H u m a n M es e nc h y m al St e m C ells f or Tr e at m e nt of Esc h eric hi a c oli E n d ot oxi n-I n d uc e d Ac ut e L u n g I nj ur y i n Mic e. St e m 
C ells Tr a nsl M e d. 2 0 1 5; 4( 7): 8 3 2- 4 0. E p u b 2 0 1 5/ 0 5/ 2 3. d oi:  1 0. 5 9 6 6/sct m. 2 0 1 5- 0 0 0 6. P u b Me d P MI D: 2 5 9 9 9 5 1 8; P M CI D: 
P M C 4 4 7 9 6 2 8. 
7 5.  
D e v a n e y J, H ori e S, M ast ers o n C, Elli m a n S, B arr y F, O' Bri e n T, C url e y G F, O' T o ol e D, L aff e y J G. H u m a n 
m es e nc h y m al str o m al c ells d ecr e as e t h e s e v erit y of ac ut e l u n g i nj ur y i n d uc e d b y E. c oli i n t h e r at. T h or ax. 
2 0 1 5; 7 0( 7): 6 2 5- 3 5. E p u b 2 0 1 5/ 0 5/ 2 0. d oi: 1 0. 1 1 3 6/ t h or axj nl- 2 0 1 5- 2 0 6 8 1 3. P u b M e d P MI D: 2 5 9 8 6 4 3 5. 
7 6.  
As m uss e n S, It o H, Tr a b er DL, L e e J W, C ox R A, H a w ki ns H K, Mc A ul e y D F, Mc K e n n a D H, Tr a b er L D, Z h u o H, Wils o n 
J, H er n d o n D N, Pr o u g h D S, Li u K D, M att h a y M A, E n k h b a at ar P. H u m a n m es e nc h y m al st e m c ells r e d uc e t h e s e v erit y of 
ac ut e l u n g i nj ur y i n a s h e e p m o d el of b act eri al p n e u m o ni a. T h or ax. 2 0 1 4; 6 9( 9): 8 1 9- 2 5. E p u b 2 0 1 4/ 0 6/ 0 4. d oi: 
1 0. 1 1 3 6/t h or axj nl- 2 0 1 3- 2 0 4 9 8 0. P u b M e d P MI D: 2 4 8 9 1 3 2 5; P M CI D: P M C 4 2 8 4 0 6 8. 
7 7.  
S h al a b y S M, El- S h al A S, A b d- All a h S H, S eli m A O, S eli m S A, G o u d a Z A, A b d El M ott el e b D M, Z a nf al y H E, El- Ass ar 
H M, A b d el azi m S. M es e nc h y m al str o m al c ell i nj ecti o n pr ot ects  a g ai nst oxi d ati v e str ess i n Esc h eric hi a c oli-i n d uc e d ac ut e 
l u n g i nj ur y i n mic e. C yt ot h er a p y. 2 0 1 4; 1 6( 6): 7 6 4- 7 5. E p u b 2 0 1 4/ 0 2/ 1 5. d oi: 1 0. 1 0 1 6/j.jc yt. 2 0 1 3. 1 2. 0 0 6. P u b M e d P MI D: 
2 4 5 2 5 1 7 3. 
7 8.  
B ust os ML, H ul ei h el L, M e y er E M , D o n n e n b er g A D, D o n n e n b er g V S, Sci ur ba J D, Mr oz L, Mc V err y BJ, Ellis B M, 
K a mi ns ki N, R oj as M. Acti v ati o n of h u m a n m es e nc h y m al st e m c ells i m p acts t h eir t h er a p e utic a biliti es i n l u n g i nj ur y b y 
i ncr e asi n g i nt erl e u ki n (IL)- 1 0 a n d IL- 1 R N l e v els. St e m C ells Tr a nsl M e d. 2 0 1 3; 2( 1 1): 8 8 4- 9 5. E p u b 2 0 1 3/ 1 0/ 0 4. d oi: 
1 0. 5 9 6 6/sct m. 2 0 1 3- 0 0 3 3. P u b M e d P M I D: 2 4 0 8 9 4 1 4; P M CI D: P M C 3 8 0 8 2 0 3. 
7 9.  
R oj as M, P ar k er R E, T h or n N, C orr e d or C, I y er S S, B u e n o M, Mr oz L, C ar d e n es N, M or a AL, St ec e n k o A A, Bri g h a m 
KL. I nf usi o n of fr es hl y is ol at e d a ut ol o g o us b o n e m arr o w d eri v e d m o n o n ucl e ar c ells pr e v e nts e n d ot oxi n-i n d uc e d l u n g 
i nj ur y i n a n ex- vi v o p erf us e d s wi n e m o d el. St e m C ell R es T h er. 2 0 1 3; 4( 2): 2 6. E p u b 2 0 1 3/ 0 3/ 1 9. d oi: 1 0. 1 1 8 6/scrt 1 7 4. 
P u b M e d P MI D: 2 3 4 9 7 7 5 5; P M CI D: P M C 3 7 0 6 9 0 6. 
8 0.  
Y a n X, F u X, Ji a Y, M a X, T a o J, Y a n g T, M a H, Li a n g X, Li u X, Y a n g J, W ei J. Nrf 2/ K e a p 1/ A R E Si g n ali n g M e di at e d a n 
A nti oxi d ati v e Pr ot ecti o n of H u m a n Pl ac e nt al M es e nc h y m al St e m C ells of F et a l Ori gi n i n Al v e ol ar E pit h eli al C ells. Oxi d 
M e d C ell L o n g e v. 2 0 1 9; 2 0 1 9: 2 6 5 4 9 1 0. E p u b 2 0 1 9/ 0 6/ 2 1. d oi: 1 0. 1 1 5 5/ 2 0 1 9/ 2 6 5 4 9 1 0. P u b M e d P MI D: 3 1 2 1 7 8 3 6; 
P M CI D: P M C 6 5 3 7 0 1 1. 
8 1.  
C ui P, Xi n H, Y a o Y, Xi a o S, Z h u F, G o n g Z, T a n g Z, Z h a n Q, Qi n W, L ai Y, Li X, T o n g Y, Xi a Z. H u m a n a m ni o n- d eri v e d 
m es e nc h y m al st e m c ells all e vi at e l u n g i nj ur y i n d uc e d b y  w hit e s m o k e i n h al ati o n i n r ats. St e m C ell R es T h er. 
2 0 1 8; 9( 1): 1 0 1. E p u b 2 0 1 8/ 0 4/ 1 4. d oi: 1 0. 1 1 8 6/s 1 3 2 8 7- 0 1 8- 0 8 5 6- 7. P u b M e d P MI D: 2 9 6 5 0 0 4 4; P M CI D: P M C 5 8 9 8 0 6 5. 
8 2.  
Z h a n g S, Ji a n g W, M a L, Li u Y, Z h a n g X, W a n g S. Nrf 2  tr a nsf ecti o n e n h a nc es t h e effic ac y of h u m a n a m ni otic 
m es e nc h y m al st e m c ells t o r e p air l u n g i nj ur y i n d uc e d b y li p o p ol ys acc h ari d e. J C ell Bi oc h e m. 2 0 1 8; 1 1 9( 2): 1 6 2 7- 3 6. E p u b 
2 0 1 7/ 0 9/ 1 5. d oi: 1 0. 1 0 0 2/jc b. 2 6 3 2 2. P u b M e d P MI D: 2 8 9 0 5 4 5 0. 
8 3.  
H u a n g Z, Li u H, Z h a n g X, W e n G, Z h u C, Z h a o Y, Ni u W, Qi n Y, C h e n H, B ai C, Li u G. Tr a nscri pt o mic a n al ysis of l u n g 
tiss u es aft er h U C- M S Cs a n d F T Y 7 2 0 tr e at me nt of li p o p ol ys acc h ari d e- i n d uc e d ac ut e l u n g i nj ur y i n m o us e m o d els. I nt 
I m m u n o p h ar m ac ol. 2 0 1 8; 6 3: 2 6- 3 4. E p u b 2 0 1 8/ 0 8/ 0 1. d oi: 1 0. 1 0 1 6/j.i nti m p. 2 0 1 8. 0 6. 0 3 6. P u b M e d P MI D: 3 0 0 6 4 0 4 0. 
8 4.  
X u a n Y Y, W u Y Y, Xi e YL, C h u J G, Li G X, W a n g L P. H u m a n M es e nc h y m al St e m/ Str o m al C ells Fr o m H u m a n U m bilic al 
C or d A m eli or at e Ac ut e R es pir at or y Distr ess S y n dr o m e i n R ats: F act ors t o C o nsi d er. Crit C ar e M e d. 2 0 1 7; 4 5( 7): e 7 3 6- e 7. 
E p u b 2 0 1 7/ 0 6/ 1 8. d oi: 1 0. 1 0 9 7/ C C M . 0 0 0 0 0 0 0 0 0 0 0 0 2 4 0 1. P u b M e d P MI D: 2 8 6 2 2 2 3 3. 
8 5.  
L e e F Y, C h e n K H, W all ac e C G, S u n g P H, S h e u JJ, C h u n g S Y, C h e n YL, L u HI, K o S F, S u n C K, C hi a n g HJ, C h a n g H W, 
L e e M S, Yi p H K. X e n o g e n eic h u m a n u m bilic al c or d- d eri v e d m es enc h y m al st e m c ells r e d uc e m o rt alit y i n r ats wit h ac ut e 
r es pir at or y distr ess s y n dr o m e c o m plic at e d b y s e psis. O nc ot ar g et. 2 0 1 7;8( 2 8): 4 5 6 2 6- 4 2. E p u b 2 0 1 7/ 0 5/ 1 0. d oi: 
1 0. 1 8 6 3 2/ o nc ot ar g et. 1 7 3 2 0. P u b M e d P MI D: 2 8 4 8 4 0 8 9; P M CI D: P M C 5 5 4 2 2 1 4. 
8 6.  
Z h u H, Xi o n g Y, Xi a Y, Z h a n g R, Ti a n D, W a n g T, D ai J, W a n g L, Y a o H, Ji a n g H, Y a n g K, Li u E, S hi Y, F u Z, G a o L, Z o u 
L. T h er a p e utic Eff ects of H u m a n U m bilic al C or d- D eri v e d M e s e nc hy m al St e m  C ells i n Ac ut e L u n g I nj ur y Mic e. Sci R e p. 
2 0 1 7; 7: 3 9 8 8 9. E p u b 2 0 1 7/ 0 1/ 0 5. d oi: 1 0. 1 0 3 8/sr e p 3 9 8 8 9. P u b M e d P MI D: 2 8 0 5 1 1 5 4; P M CI D: P M C 5 2 0 9 6 8 5. 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
5 7 | P a g e  
 
 
C o nfi de ntial
  
8 7.  
C url e y G F, J er kic M, Dix o n S, H o g a n G, M ast ers o n C, O' T o ol e D, D e v a n e y J, L aff e y J G. Cr y o pr es er v e d, X e n o- Fr e e 
H u m a n U m bilic al C or d M es e nc h y m al Str o m al C ells R e d uc e L u n g I nj ur y S e v erit y a n d B act eri al B ur d e n i n R o d e nt 
Esc h eric hi a c oli-I n d uc e d Ac ut e R es pir at or y Distr ess S y n dr o m e. Crit C ar e M e d.  2 0 1 7; 4 5( 2): e 2 0 2- e 1 2. E p u b 2 0 1 6/ 1 1/ 2 0. 
d oi: 1 0. 1 0 9 7/ C C M. 0 0 0 0 0 0 0 0 0 0 0 0 2 0 7 3. P u b M e d P MI D: 2 7 8 6 1 1 8 2. 
8 8.  
C h a n g Y, P ar k S H, H u h J W, Li m C M, K o h Y, H o n g S B. I ntr atr ac h e al a d mi nistr ati o n of u m bilic al c or d bl o o d- d eri v e d 
m es e nc h y m al st e m c ells i n a p ati e nt wit h ac ut e r es pir at or y distr ess s y n dr o m e. J K or e a n M e d Sci. 2 0 1 4; 2 9( 3): 4 3 8- 4 0. 
E p u b 2 0 1 4/ 0 3/ 1 3. d oi: 1 0. 3 3 4 6/j k ms. 2 0 1 4. 2 9. 3. 4 3 8.  P u b M e d P MI D: 2 4 6 1 6 5 9 6; P M CI D: P M C 3 9 4 5 1 4 2. 
8 9.  
M o o dl e y Y, Ati e nz a D, M a n u el pill ai U, S a m u el C S, Tc h o n g u e J, Il a nc h er a n S, B o y d R, Tr o u ns o n A. H u m a n 
u m bilic al c or d m es e nc h y m al st e m c ells r e d uc e fi br osis of  bl e o m yci n-i n d uc e d l u n g i nj ur y. A m J P at h ol. 2 0 0 9; 1 7 5( 1): 3 0 3-
1 3. E p u b 2 0 0 9/ 0 6/ 0 6. d oi: 1 0. 2 3 5 3/ aj p at h. 2 0 0 9. 0 8 0 6 2 9. P u b M e d P MI D: 1 9 4 9 7 9 9 2; P M CI D: P M C 2 7 0 8 8 1 6. 
9 0.  
Xi a n g B, C h e n L, W a n g X, Z h a o Y, W a n g Y, Xi a n g C. Tr a ns pl a nt ati o n of M e nstr u al Bl o o d- D eri v e d M es e nc h y m al 
St e m C ells Pr o m ot es t h e R e p air of L P S-I n d uc e d Ac ut e L u n g I nj ur y. I nt J M ol Sci. 2 0 1 7; 1 8( 4). E p u b 2 0 1 7/ 0 3/ 2 8. d oi: 
1 0. 3 3 9 0/ij ms 1 8 0 4 0 6 8 9. P u b M e d P MI D: 2 8 3 4 6 3 6 7; P M CI D: P M C 5 4 1 2 2 7 5. 
9 1.  
W a n g L, S hi M, T o n g L, W a n g J, Ji S, Bi J, C h e n C, Ji a n g J, B ai C, Z h o u J, S o n g Y. L u n g- R esi d e nt M es e nc h y m al St e m 
C ells Pr o m ot e R e p air of L P S-I n d uc e d Ac ut e L u n g I nj ur y vi a R e g ul ati n g t h e B al a nc e of R e g ul a t or y T c ells a n d T h 1 7 c ells. 
I nfl a m m ati o n. 2 0 1 9; 4 2( 1): 1 9 9- 2 1 0. E p u b 2 0 1 8/ 0 9/ 0 7. d oi: 1 0. 1 0 0 7/s 1 0 7 5 3- 0 1 8- 0 8 8 4- 6. P u b M e d P MI D: 3 0 1 8 7 3 3 7. 
9 2.  
Sil v a J D, L o p es- P ac h ec o M, P az A H R, Cr uz F F, M el o E B, d e Oli v eir a M V, Xist o D G, C a p el ozzi VL, M or al es M M, 
P el osi P, Cir n e-Li m a E, R occ o P R M. M es e nc h y m al St e m C ells Fr o m B o n e M arr o w, A di p os e Tiss u e, a n d L u n g Tiss u e 
Diff er e nti all y Miti g at e L u n g a n d Dist al Or g a n D a m a g e i n Ex p eri m e nt al Ac ut e R es pir at or y Distr ess S y n dr o m e. Crit C ar e 
M e d. 2 0 1 8; 4 6( 2): e 1 3 2- e 4 0. E p u b 2 0 1 7/ 1 1/ 0 9. d o i: 1 0. 1 0 9 7/ C C M. 0 0 0 0 0 0 0 0 0 0 0 0 2 8 3 3. P u b M e d P MI D: 2 9 1 1 6 9 9 8. 
9 3.  
S u V Y, Li n C S, H u n g S C, Y a n g K Y. M es e nc h y m al St e m C ell- C o n diti o n e d M e di u m I n d uc es N e utr o p hil A p o pt osis 
Ass oci at e d wit h I n hi biti o n of t h e N F- k a p p a B P at h w a y i n E n d ot oxi n- I n d uc e d Ac ut e L u n g I nj ur y. I nt J M ol Sci. 2 0 1 9; 2 0( 9). 
E p u b 2 0 1 9/ 0 5/ 0 8. d oi: 1 0. 3 3 9 0/ij ms 2 0 0 9 2 2 0 8. P u b M e d P MI D: 3 1 0 6 0 3 2 6; P M CI D: P M C 6 5 4 0 3 5 3. 
9 4.  
M o h a m m a di p o or A, A nt e bi B, B atc hi ns k y AI, C a nci o  L C. T h er a p e utic p ot e nti al of pr o d ucts d eri v e d fr o m 
m es e nc h y m al st e m/str o m al c ells i n  p ul m o n ar y dis e as e. R es pir R es. 2 0 1 8; 1 9( 1): 2 1 8. E p u b 2 0 1 8/ 1 1/ 1 1. d oi: 
1 0. 1 1 8 6/s 1 2 9 3 1- 0 1 8- 0 9 2 1-x. P u b M e d P MI D: 3 0 4 1 3 1 5 8; P M CI D: P M C 6 2 3 4 7 7 8. 
9 5.  
L e e J H, P ar k J, L e e J W. T h er a p e utic us e of m es e nc h y m al st e m c ell- d eri v e d extr ac ell ul ar v esicl es i n ac ut e l u n g 
i nj ur y. Tr a nsf usi o n. 2 0 1 9; 5 9( S 1): 8 7 6- 8 3. E p u b 2 0 1 8/ 1 1/ 0 2. d oi: 1 0. 1 1 1 1/trf. 1 4 8 3 8. P u b M e d P MI D: 3 0 3 8 3 8 9 5; P M CI D: 
P M C 6 3 6 8 8 8 9. 
9 6.  
A br e u S C, W eiss DJ, R occ o P R. Extr ac ell ul ar v esicl es d eri v e d fr o m m es e nc h y m al str o m al c ells: a t h er a p e utic 
o pti o n i n r es pir at or y dis e as es ? St e m C ell R es T h er. 2 0 1 6; 7( 1): 5 3. E p u b 2 0 1 6/ 0 4/ 1 5. d oi: 1 0. 1 1 8 6/s 1 3 2 8 7- 0 1 6- 0 3 1 7- 0. 
P u b M e d P MI D: 2 7 0 7 5 3 6 3; P M CI D: P M C 4 8 3 1 1 7 2. 
9 7.  
M o ns el A, Z h u Y G, G u d a p ati V, Li m H, L e e J W. M es e nc h y m al st e m c ell d eri v e d s ecr et o m e a n d extr ac ell ul ar 
v esicl es f or ac ut e l u n g i nj ur y a n d ot h er i nfl a m m at or y l u n g dis e as es. Ex p ert O pi n Bi ol T h er. 2 0 1 6; 1 6( 7): 8 5 9- 7 1. E p u b 
2 0 1 6/ 0 3/ 2 5. d oi: 1 0. 1 5 1 7/ 1 4 7 1 2 5 9 8. 2 0 1 6. 1 1 7 0 8 0 4. P u b M e d P MI D: 2 7 0 1 1 2 8 9; P M CI D: P M C 5 2 8 0 8 7 6. 
9 8.  
Li u F B, Li n Q, Li u Z W. A st u d y o n t h e r ol e of a p o p t otic h u m a n u m bilic al c or d m es e nc h y m al st e m c ells i n 
bl e o m yci n-i n d uc e d ac ut e l u n g i nj ur y i n r at m o d els. E u r R e v M e d P h ar m ac ol Sci. 2 0 1 6; 2 0( 5): 9 6 9- 8 2. E p u b 2 0 1 6/ 0 3/ 2 5. 
P u b M e d P MI D: 2 7 0 1 0 1 5 8. 
9 9.  
C h e n J, Li Y, H a o H, Li C, D u Y, H u Y, Li J, Li a n g Z, Li C, Li u J, C h e n L. M es e nc h y m al St e m C ell C o n diti o n e d M e di u m 
Pr o m ot es Pr olif er ati o n a n d Mi gr ati o n of Al v e ol ar E pit h eli al C ells u n d er S e ptic C o n diti o ns I n Vitr o vi a t h e J N K- P 3 8 
Si g n ali n g P at h w a y. C ell P h ysi ol Bi oc h e m. 2 0 1 5; 3 7( 5) : 1 8 3 0- 4 6. E p u b 2 0 1 5/ 1 1/ 2 0. d oi: 1 0. 1 1 5 9/ 0 0 0 4 3 8 5 4 5. P u b M e d 
P MI D: 2 6 5 8 4 2 8 3. 
1 0 0.  
I o n esc u L, B yr n e R N, v a n H a aft e n T, V a di v el A, Al p h o ns e R S, R e y- P arr a GJ, W eiss m a n n G, H all A, E at o n F, 
T h e b a u d B. St e m c ell c o n diti o n e d m e di u m i m pr o v es ac ut e l u n g  i nj ur y i n mic e: i n vi v o e vi d e nc e f or st e m c ell p ar acri n e 
acti o n. A m J P h ysi ol L u n g C ell M ol P h ysi ol. 2 0 1 2; 3 0 3( 1 1):L 9 6 7- 7 7. E p u b 2 0 1 2/ 1 0/ 0 2. d oi: 1 0. 1 1 5 2/ aj pl u n g. 0 0 1 4 4. 2 0 1 1. 
P u b M e d P MI D: 2 3 0 2 3 9 7 1; P M CI D: P M C 3 5 3 2 5 2 3. 
1 0 1.  
C h e n g SL, Li n C H, Y a o CL. M es e nc h y m al St e m C ell A d mi ni str ati o n i n P ati e nts wit h C hr o nic O bstr ucti v e P ul m o n ar y 
Dis e as e: St at e of t h e Sci e nc e. St e m C ells I nt. 2 0 1 7; 2 0 1 7: 8 9 1 6 5 7 0. E p u b 2 0 1 7/ 0 3/ 1 8. d oi: 1 0. 1 1 5 5/ 2 0 1 7/ 8 9 1 6 5 7 0. 
P u b M e d P MI D: 2 8 3 0 3 1 5 4; P M CI D: P M C 5 3 3 7 8 7 8. 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
5 8 | P a g e  
 
 
C o nfi de ntial
  
1 0 2.  
G o nz al ez R, Gri p aric L, U m a n a M, B ur g e e K, V ar g as V,  N asr all a h R, Sil v a F, P at el A. A n effici e nt a p pr o ac h t o 
is ol ati o n a n d c h ar act eriz ati o n of pr e- a n d p ost n at al u m bilical c or d li ni n g st e m c ells f o r cli nic al a p plic ati o ns. C ell 
Tr a ns pl a nt. 2 0 1 0; 1 9( 1 1): 1 4 3 9- 4 9. E p u b 2 0 1 0/ 0 7/ 0 1.  d oi: 1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 0 X 5 1 4 2 6 0. P u b M e d P MI D: 2 0 5 8 7 1 3 6. 
1 0 3.  
B a ks h D, S o n g L, T u a n R S. A d ult m es e nc h y m al st e m c ells : c h ar act eriz ati o n, diff er e nti ati o n, a n d a p plic ati o n i n c ell 
a n d g e n e t h er a p y. J C ell M ol M e d. 2 0 0 4; 8( 3): 3 0 1- 1 6. E p u b 2 0 0 4/ 1 0/ 2 0. d oi: 1 0. 1 1 1 1/j. 1 5 8 2- 4 9 3 4. 2 0 0 4.t b 0 0 3 2 0.x. 
P u b M e d P MI D: 1 5 4 9 1 5 0 6; P M CI D: P M C 6 7 4 0 2 2 3. 
1 0 4.  
B a ks h D, Y a o R, T u a n R S. C o m p aris o n of pr olif er at i v e a n d m ultili n e a g e diff er e nti ati o n p ot e nti al of h u m a n 
m es e nc h y m al st e m c ells d eri v e d fr o m u m bilic al c or d a n d b o n e m arr o w. St e m C ells. 2 0 0 7; 2 5( 6): 1 3 8 4- 9 2. E p u b 
2 0 0 7/ 0 3/ 0 3. d oi: 1 0. 1 6 3 4/st e mc ells. 2 0 0 6- 0 7 0 9. P u b M e d P MI D: 1 7 3 3 2 5 0 7. 
1 0 5.  
P ar oli ni O, Al vi a n o F, B a g n ar a G P, B ilic G, B u hri n g HJ, E v a n g elist a M, H e n n er bic hl er S, Liu B, M a g atti M, M a o N, 
Mi ki T, M ar o n gi u F, N a k aji m a H, Ni k ai d o T, P ort m a n n-L a nz C B , S a n k ar V, S o nci ni M, St a dl er G, S ur b e k D, T a k a h as hi T A, 
R e dl H, S a k ur a g a w a N, W ol b a n k S, Z eis b er g er S, Zisc h A, St r o m S C. C o ncis e r e vi e w: is ol ati o n a n d c h ar act eriz ati o n of c ells 
fr o m h u m a n t er m pl ac e nt a: o utc o m e of t h e first i nt er n ati o n al W or ks h o p o n Pl ac e nt a D eri v e d St e m C ells. St e m C ells. 
2 0 0 8; 2 6( 2): 3 0 0- 1 1. E p u b 2 0 0 7/ 1 1/ 0 3. d oi: 1 0. 1 6 3 4/ st e mc ells. 2 0 0 7- 0 5 9 4. P ub M e d P MI D: 1 7 9 7 5 2 2 1. 
1 0 6.  
Ki m K, B o u- G h a n n a m S, T h or p H, Gr ai n g er D W, O k a n o T. H u m a n m es e nc h y m al st e m c ell s h e ets i n x e n o-fr e e 
m e di a f or p ossi bl e all o g e nic a p plic ati o ns. Sci R e p. 2 0 1 9; 9( 1): 1 4 4 1 5. E p u b 2 0 1 9/ 1 0/ 0 9. d oi: 1 0. 1 0 3 8/s 4 1 5 9 8- 0 1 9- 5 0 4 3 0-
7. P u b M e d P MI D: 3 1 5 9 5 0 1 2. 
1 0 7.  
H a m mi n g I, Ti m e ns W, B ult h uis ML, L el y A T, N a vis G, v a n G o or H. Tiss u e distri b uti o n of A C E 2 pr ot ei n, t h e 
f u ncti o n al r ec e pt or f or S A R S c or o n a vir us. A first st e p i n u n d erst a n di n g S A R S p at h o g e n esis. J P at h ol. 2 0 0 4; 2 0 3( 2): 6 3 1- 7. 
E p u b 2 0 0 4/ 0 5/ 1 4. d oi: 1 0. 1 0 0 2/ p at h . 1 5 7 0. P u b M e d P MI D: 1 5 1 4 1 3 7 7. 
1 0 8.  
Ji a H P, L o o k D C, S hi L, Hic k e y M, P e w e L, N etl a n d J,  F arz a n M, W o hlf or d-L e n a n e C, P erl m a n S, Mc Cr a y P B, Jr. 
A C E 2 r ec e pt or ex pr essi o n a n d s e v er e ac ut e r es pir at or y s y n dr o m e c or o n a vir us i nf ecti o n d e p e n d o n diff er e nti ati o n of 
h u m a n air w a y e pit h eli a. J Vir ol. 2 0 0 5; 7 9( 2 3): 1 4 6 1 4- 2 1. E p u b 2 0 0 5/ 1 1/ 1 2. d oi: 1 0. 1 1 2 8/J VI. 7 9. 2 3. 1 4 6 1 4- 1 4 6 2 1. 2 0 0 5. 
P u b M e d P MI D: 1 6 2 8 2 4 6 1; P M CI D: P M C 1 2 8 7 5 6 8. 
1 0 9.  
R oj e ws ki M T, F e k et e N, B ail a S, N g u y e n K, F urst D, A nt wil er D, D a us e n d J, Kr ej a L, I g n ati us A, S e ns e b e L, 
Sc hr ez e n m ei er H. G M P-c o m pli a nt is ol at i o n a n d ex p a nsi o n of b o n e m arr o w- d eri v e d M S Cs i n t h e cl os e d, a ut o m at e d 
d e vic e q u a nt u m c ell ex p a nsi o n s yst e m. C ell Tr a ns pl a nt. 2 0 1 3; 2 2( 1 1): 1 9 8 1- 2 0 0 0. d oi: 1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 2 X 6 5 7 9 9 0. 
P u b M e d P MI D: 2 3 1 0 7 5 6 0. 
1 1 0.  
B ai J, H u Y, W a n g Y R, Li u L F, C h e n J, S u S P, W a n g Y. C o m p aris o n of h u m an a m ni otic fl ui d- d eri v e d a n d u m bilic al 
c or d W h art o n's J ell y- d eri v e d m es e nc h y m al str o m al c ells: C h ar act eriz ati o n a n d m y oc ar di al diff er e nti ati o n c a p acit y. J 
G eri atr C ar di ol. 2 0 1 2; 9( 2): 1 6 6- 7 1. d oi: 1 0. 3 7 2 4/ S P.J . 1 2 6 3. 2 0 1 1. 1 2 0 9 1. P u b M e d P MI D: 2 2 9 1 6 0 6 4; P M CI D: P M C 3 4 1 8 9 0 7. 
1 1 1.  
B ar b a d o J, T a b er a S, S a nc h ez A, G arci a- S a nc h o J. T h er a p e utic p ot e nti al of  all o g e n eic m es e nc h y m al str o m al c ells 
tr a ns pl a nt ati o n f or l u p us n e p hritis. L u p us. 2 0 1 8; 2 7( 1 3): 2 1 6 1- 5. E p u b 2 0 1 8/ 1 0/ 0 7. d oi: 1 0. 1 1 7 7/ 0 9 6 1 2 0 3 3 1 8 8 0 4 9 2 2. 
P u b M e d P MI D: 3 0 2 9 0 7 1 7. 
1 1 2.  
S ui W, H o u X, C h e W, C h e n J, O u M, X u e W, D ai Y. H e m at o p oi etic a n d m es e nc h y m al st e m c ell tr a ns pl a nt ati o n f or 
s e v er e a n d r efr act or y s yst e mic l u p us er yt h e m at os us. Cli n I m m u n ol. 2 0 1 3; 1 4 8( 2): 1 8 6- 9 7. E p u b 2 0 1 3/ 0 6/ 1 9. d oi: 
1 0. 1 0 1 6/j.cli m. 2 0 1 3. 0 5. 0 1 4. P u b M e d P MI D: 2 3 7 7 0 6 2 8. 
1 1 3.  
W a n g D, Li J, Z h a n g Y, Z h a n g M, C h e n J, Li X, H u X, Ji a n g S, S hi S, S u n L. U m bilic al c or d m es e nc h y m al st e m c ell 
tr a ns pl a nt ati o n i n acti v e a n d r efr act or y s yst e mic l u p us er yth e m at os us: a m ultic e nt er cli nic al st u d y. Art hritis R es T h er. 
2 0 1 4; 1 6( 2): R 7 9. d oi: 1 0. 1 1 8 6/ ar 4 5 2 0. P u b M e d P MI D: 2 4 6 6 1 6 3 3; P M CI D: P M C 4 0 6 0 5 7 0. 
1 1 4.  
W a n g D, Ni u L, F e n g X, Y u a n X, Z h a o S, Z h a n g H, Li a n g J, Z h a o C, W a n g H, H u a B, S u n L. L o n g-t er m s af et y of 
u m bilic al c or d m es e nc h y m al st e m c ells tr a ns pl a nt ati o n f or s y st e mic l u p us er yt h e m at os us: a 6- y e ar f oll o w- u p st u d y. Cli n 
Ex p M e d. 2 0 1 7; 1 7( 3): 3 3 3- 4 0. d oi: 1 0. 1 0 0 7/s 1 0 2 3 8- 0 1 6- 0 4 2 7- 0. P u b M e d P MI D: 2 7 2 7 0 7 2 9. 
1 1 5.  
M a h d a vi G or a bi A, B a n ac h M, R ei n er Z, Pirr o M, H aji g h as e mi S, J o h nst o n T P, S a h e b k ar A. T h e R ol e of 
M es e nc h y m al St e m C ells i n At h er oscl er osi s: Pr os p ects f or T h er a p y vi a t h e M o d ul ati o n of I nfl a m m at or y Mili e u. J Cli n 
M e d. 2 0 1 9; 8( 9). E p u b 2 0 1 9/ 0 9/ 1 1. d oi: 1 0. 3 3 9 0/jc m 8 0 9 1 4 1 3. P u b M e d P MI D: 3 1 5 0 0 3 7 3; P M CI D: P M C 6 7 8 0 1 6 6. 
1 1 6.  
Ts ai PJ, W a n g H S, Li n GJ, C h o u S C, C h u T H, C h u a n W T, L u YJ, W e n g Z C, S u C H, Hsi e h P S, S yt w u H K, Li n C H, C h e n 
T H, S h y u J F. U n diff er e nti at e d W h art o n's J ell y M es e nc h y m al St e m  C ell Tr a ns pl a nt ati o n I n d uc es I ns uli n- Pr o d uci n g C ell 
Diff er e nti ati o n a n d S u p pr essi o n of T- C ell- M e di at e d A ut o i m m u nit y i n N o n o b es e Di a b etic Mic e. C ell Tr a ns pl a nt. 
2 0 1 5; 2 4( 8): 1 5 5 5- 7 0. d oi: 1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 4 X 6 8 3 0 1 6. P u b M e d P MI D: 2 5 1 9 8 1 7 9. 

U C- M S Cs i n C O VI D- 1 9  
 
S p o ns or-I n vesti gat or: Pr of. Ca mill o Ric or di, M. D., F N A I
 
5 9 | P a g e  
 
 
C o nfi de ntial
  
1 1 7.  
W a n g H S, S h y u J F, S h e n W S, Hs u H C, C hi T C, C h e n C P, H u a n g S W, S h yr Y M, T a n g K T, C h e n T H. Tr a ns pl a nt ati o n of 
i ns uli n- pr o d uci n g c ells d eri v e d fr o m u m bilic al c or d str o m al m es e nc h y m al st e m c ells t o tr e at N O D mic e. C ell Tr a ns pl a nt. 
2 0 1 1; 2 0( 3): 4 5 5- 6 6. d oi: 1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 0 X 5 2 2 2 7 0. P u b M e d P MI D: 2 0 7 1 9 0 8 6. 
1 1 8.  
H u J, W a n g Y, W a n g F, W a n g L, Y u X,  S u n R, W a n g Z, W a n g L, G a o H, F u Z, Z h a o W, Y a n S. Eff ect a n d m ec h a nis ms 
of h u m a n W h art o n's j ell y- d eri v e d m es e nc h y m al st e m c ells o n t y p e 1 di a b et es i n N O D m o d el. E n d ocri n e. 2 0 1 5; 4 8( 1): 1 2 4-
3 4. d oi: 1 0. 1 0 0 7/s 1 2 0 2 0- 0 1 4- 0 2 1 9- 9. P u b M e d P MI D: 2 4 5 9 0 2 9 4. 
1 1 9.  
S or di V, M al osi o ML, M arc h esi F, M erc alli A, M elzi R, Gi or d a n o T, B el m o nt e N, F err ari G, L e o n e B E, B ert uzzi F, 
Z er bi ni G, All a v e n a P, B o nif aci o E, Pi e m o nti L. B o n e m arr o w m es e nc h y m al st e m c ells ex pr ess a r estrict e d s et of 
f u ncti o n all y acti v e c h e m o ki n e r ec e pt ors c a p a bl e of pr o m oti n g mi gr ati o n t o p ancr e atic isl ets. Bl o o d. 2 0 0 5; 1 0 6( 2): 4 1 9- 2 7. 
d oi: 1 0. 1 1 8 2/ bl o o d- 2 0 0 4- 0 9- 3 5 0 7.  P u b M e d P MI D: 1 5 7 8 4 7 3 3. 
1 2 0.  
Ez q u er F E, Ez q u er M E, P arr a u D B, C ar pi o D, Y a n ez AJ, C o n g et P A. S yst e mic a d mi ni str ati o n of m ulti p ot e nt 
m es e nc h y m al str o m al c ells r e v erts h y p er gl yc e mi a a n d pr e v e nts n e p hr o p at h y i n t y p e 1 di a b etic mic e. Bi ol Bl o o d M arr o w 
Tr a ns pl a nt. 2 0 0 8; 1 4( 6): 6 3 1- 4 0. d oi: 1 0. 1 0 1 6/j. b b mt. 2 0 0 8. 0 1. 0 0 6. P u b M e d P MI D: 1 8 4 8 9 9 8 8. 
1 2 1.  
B oc elli- T y n d all C, Br acci L, S p a g n oli G, Br acci ni A, B o uc h e n a ki M, C er e di g R, Pist oi a V, M arti n I,  T y n d all A. B o n e 
m arr o w m es e nc h y m al str o m al c ells ( B M- M S Cs) fr o m h e alt h y d o n ors a n d a ut o-i m m u n e dis e as e p ati e nts r e d uc e t h e 
pr olif er ati o n of a ut ol o g o us- a n d all o g e n eic-sti m ul at e d l y m p h oc yt es i n vitr o. R h e u m at ol o g y ( Oxf or d). 2 0 0 7; 4 6( 3): 4 0 3- 8. 
E p u b 2 0 0 6/ 0 8/ 2 2. d oi: 1 0. 1 0 9 3/r h e u m at o l o g y/ k el 2 6 7. P u b M e d P MI D: 1 6 9 2 0 7 5 0. 
1 2 2.  
Wi nt ers A A, B o u- G h a n n a m S, T h or p H, H a w a y e k J A, At ki ns o n DL, B artl ett C E, Sil v a FJ, Hs u E W, M or e n o A P, 
Gr ai n g er D A, P at el A N. E v al u ati o n of M ulti pl e Bi ol o gic al T h er a pi es f or Isc h e mic C ar di ac Dis e as e. C ell Tr a ns pl a nt. 
2 0 1 6; 2 5( 9): 1 5 9 1- 6 0 7. d oi: 1 0. 3 7 2 7/ 0 9 6 3 6 8 9 1 6 X 6 9 1 5 0 1. P u b M e d P MI D: 2 7 1 6 5 3 7 0. 
 
 

T hi s i s a r e pr e s e nt ati o n of a n el e ctr o ni c r e c or d t h at w a s si g n e d
el e ctr o ni c all y.
T hi s p a g e i s t h e m a nif e st ati o n of t h e el e ctr o ni c si g n at ur e( s).