The Effect of Micro Fragmented Adipose Tissue (MFAT) on Knee Osteoarthritis
Phase: PHASE3
Conditions: Osteoarthritis, Knee, Knee Pain
Sponsor: Stanford University

 
 
 
 
 
The Effect of Micro Fragmented Adipose Tissue (MFAT) 
on Knee Osteoarthritis 
 
Study Protocol 
NCT03467919 
December 8, 2020 
 
 
 

1) Name of study  
 
Micro Fragmented Fat Tissue on Knee Osteoarthritis 
 
2) PI and other key investigators or key study personnel 
Co-PI: Eugene Y. Roh, MD and Seth Sherman, MD 
Research coordinator: Jessica Nguyen, CRCA 
 
3) Specific source of institutional funding (account number) 
Internal funding from Charity 
 
4) List of sources from whom you are seeking funds (or have sought funding) 
for this project 
AMSSM funding 
Stanford internal funding 
PM&R foundation 
Charity from donors 
 
5) Specific aims and basic hypothesis including an explicit primary hypothesis 
or goal 
 
Microfragmented Adipose Tissue (MFAT) may be beneficial to patients with OA because 
they may differentiate into chondrocytes, promote endogenous tissue repair, and have 
potent anti-inflammatory properties.  
We aim to determine whether MFAT injection as an alternative therapy in patients with 
degenerative arthritis will result in improved clinical outcomes and structural improvement 
compared to conventional therapy. 
 
Hypothesis: 
Intraarticular injection of Microfragmented Adipose Tissue (MFAT) into the knee of patients 
with symptomatic moderate osteoarthritis will improve patient-reported outcomes of pain 
and function better compared to a conventional intra articular steroid injection. 
 
6) General background (2 page maximum including published preclinical and 
animal data supporting basic hypothesis, if relevant) 
Preliminary studies of Mesenchymal stem cell (MSC) therapy in osteoarthritic patients have 
generally shown positive results, albeit in uncontrolled studies. Jo et al injected ADSCs into 
osteoarthritic knees, finding the procedure to be safe and effective at 6-month follow-up in 
18 patients; no adverse reactions were noted while WOMAC scores and cartilage volume 
increased.  
 
A large study by Michalek et al in 1128 patients also showed no adverse events with ADSC 
injection into knee and hip joints with at least 50% score improvement in 91% of patients at 
12-month follow-up. (Michalek 2015)  

Koh et al treated 30 patients ith knee OA (age > 65) by injecting ADSCs obtained using 
liposuction techniques. Eighty-four percent (84%) had no worsening of radiographic OA at 2 
years following ADSC injection, and 88% of patients that consented to a second-look 
arthroscopic procedure improved or maintained their cartilage status at least 2 years 
following ADSC injection. (Koh 2015) 
 
7) Preliminary unpublished data (1 page maximum)  
 
N/A 
 
8) Experimental design and data analysis, including inclusion and exclusion 
criteria, statistical basis for the number of subjects to be enrolled, the 
statistical plan for analyzing at least the primary hypothesis, matrix showing 
procedure plan for each study visit, data safety monitoring plan (4 pages 
maximum) 
 
design 
Randomized double blinded study.  
 
Data analysis 
-t test  
 
 
Inclusion Criteria 
- Age between 25 and 75 years-old 
- Diagnosis of pre-existing osteoarthritis of the joint by Kellegren-Lawrence Grade 2 or 3. 
- Working understanding of the English language and able to fully understand the procedure 
- Capable of providing informed consent 
- Able to complete online, in-person or phone surveys for the purposes of follow-up 
- Capable of understanding pre- and post-procedure care instructions 
- Ambulatory at baseline 
- Previous trial and failure of conservative therapy consisting of a minimum of 6 weeks of 
physical therapy and trial of anti-inflammatory medications if not contraindicated, with or 
without concomitant bracing and/or injections. 
 
 
data safety monitoring  
Redcap will be used as a secure database in which to compile and  
capture all data.  
All data will be entered directly to the Redcap database. Data will  
be de- identified and coded through Redcap prior to exportation to spreadsheet form for 
data analysis. 
 
 

procedure plan 
 
Time of Visit 
Knee Exam 
Questionnaires 
X-Ray 
MRI 
Baseline 
Standard care 
Study 
Standard care 
Standard care 
 
Injection 
Study 
Study 
N/A 
N/A 
1 month (±1w) 
Standard care 
Standard care 
 
N/A 
N/A 
 
6 weeks (±1w) 
N/A 
N/A 
N/A 
Study 
3months (±4w) 
Standard care 
Standard care 
 
N/A 
N/A 
 
6 months (±4w) 
Standard care 
Standard care 
 
N/A 
N/A 
 
12 months (±2mos.) 
Standard care 
Standard care 
 
N/A 
Study 
24 months (±2mos.) 
Standard care 
Standard care 
 
N/A 
N/A 
 
 
 
 
 
 
 
Exclusion Criteria 
 
-Age < 25 or > 75 years old 
- Radiographs demonstrating either no, little or severe osteoarthritis (Kellegren-Lawrence 
Grade 0, 1 ) 
-Prior total or partial joint replacement surgery or a surgery involving cartilage regeneration 
(microfracture, ACI, etc) 
-Previous cortisone and/or Hyaluronic acid or PRP(Platelet rich plasma) intra-articular 
injection within the last 3 months 
- Co-morbiditiy with rheumatologic condition, inflammatory arthritis 
- Currently undergoing immunomodulatory therapy 
- Uncontrolled endocrine disorder 
- BMI >35  
- Current diagnosis of osteomyelitis, human immunodeficiency virus (HIV-1, -2) and/or 
hepatitis C (HCV), infection and poorly controlled diabetes (HgA1C >7.0) 
- Pregnancy or planned pregnancy 
- previous stem cell injection into treatment joint 
- Patient scheduled to undergo any concomitant surgical procedures. 
- Coagulopathy or anticoagulant treatment 
- Chronic pain involving multiple body parts or opioid medication management 
 
9) Significance 
 
Osteoarthritis (OA) is a leading cause of morbidity in the United States, causing pain and 
impaired physical function at an individual level, along with significant economic burden of 

disease at a population level. Regenerative medicine, specifically through the use of 
mesenchymal stem cells (MSCs), presents novel and promising therapies to aid in treating 
this ubiquitous disease. However, it should be pointed out that there is no strong evidence 
of stem cell treatment of knee OA treatment. Early studies investigating the effects of MSCs 
in the setting of OA have noted a dual benefit to stem cell therapy, which includes both 
tissue restoration and inflammation-reduction. MSCs have shown some promise to directly 
restore cartilage defects in animal models. Early clinical trials of adipose-derived stem cells 
(ADSCs), an easily harvested source of MSCs, have shown encouraging results but no 
randomized controlled trials have been published. This study aims to evaluate the efficacy 
of MFAT therapy, in conjunction with growth factors from platelet-rich plasma, on 
osteoarthritis compared to conventional treatment in a randomized controlled trial. 
 
10) Key References 
 
• Abumaree M, Al Jumah M, Pace RA, Kalionis B. Immunosuppressive properties of 
mesenchymal stem cells. Stem cell reviews. 2012;8(2):375-92. 
• Bedi A, Feeley BT, Williams RJ, 3rd. Management of articular cartilage defects of the 
knee. J Bone Joint Surg Am. 2010;92(4):994-1009. 
• Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis research & 
therapy. 2008;10(5):223. 
• Cui L, Wu Y, Cen L, Zhou H, Yin S, Liu G, et al. Repair of articular cartilage defect in 
non-weight bearing areas using adipose derived stem cells loaded polyglycolic acid 
mesh. Biomaterials. 2009;30(14):2683-93. 
• Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, et al. Intra-articular 
delivery of adipose derived stromal cells attenuates osteoarthritis progression in an 
experimental rabbit model. Arthritis research & therapy. 2013;15(1):R22. 
• Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of 
the current status and prospects. Osteoarthritis and cartilage / OARS, Osteoarthritis 
Research Society. 2002;10(6):432-63. 
• Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look 
arthroscopic findings after treatment with adipose-derived stem cells for knee 
osteoarthritis. Knee surgery, sports traumatology, arthroscopy : official journal of the 
ESSKA. 2015;23(5):1308-16. 
• Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of 
the prevalence of arthritis and other rheumatic conditions in the United States. Part 
II. Arthritis and rheumatism. 2008;58(1):26-35. 
• Mandle R. Analysis of Emcyte Corporation Concentrating Systems: An independent 
review of pre-clinical performance data. Boston, MA2012. 
• Michalek J, Moster R, Lukac L, Proefrock K, Petrasovic M, Rybar J, et al. Autologous 
adipose tissue-derived stromal vascular fraction cells application in patients with 
osteoarthritis. Cell transplantation. 2015. 
• Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of 
osteoarthritis. Arthritis and rheumatism. 2003;48(12):3464-74. 
• Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, et al. Interleukin 1 
receptor antagonist mediates the antiinflammatory and antifibrotic effect of 

mesenchymal stem cells during lung injury. Proceedings of the National Academy of 
Sciences of the United States of America. 2007;104(26):11002-7. 
• Paradowski PT, Bergman S, Sunden-Lundius A, Lohmander LS, Roos EM. Knee 
complaints vary with age and gender in the adult population. Population-based 
reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). BMC 
musculoskeletal disorders. 2006;7:38. 
• Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): 
from joint injury to osteoarthritis. Health and quality of life outcomes. 2003;1:64. 
• ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. 
Antiinflammatory and chondroprotective effects of intraarticular injection of 
adipose-derived stem cells in experimental osteoarthritis. Arthritis and rheumatism. 
2012;64(11):3604-13.