Adipose Derived Stromal Cell Transplantation as an Adjunct to Arthroscopy in Treatment of Effusion Synovitis of the Early Degenerative Knee
Phase: PHASE4
Conditions: Knee Osteoarthritis
Sponsor: Hospital for Special Surgery, New York

Study Protocol  
TITLE: Adipose Derived Stromal Cell Transplantation as an Adjunct to Arthroscopy in Treatment of 
Effusion Synovitis of the Early Degenerative Knee  
 
NCT NUMBER: NCT03922490 
 
DATE OF DOCUMENT: JUNE 16, 2022  
 
 

Study Protocol: Adipose Derived Stromal Cell Transplantation as an Adjunct to Arthroscopy in 
Treatment of Effusion Synovitis of the Early Degenerative Knee 
 
Abstract: 
 
This is a prospective study that will evaluate the early clinical outcomes of adipose-derived 
stromal cell injection plus arthroscopic debridement in the management of symptomatic effusion 
synovitis in patients with meniscal tears and knee osteoarthritis. There has been increasing focus 
on the use of mesenchymal stromal cells (MSCs) in the management of knee joint pathology 
including early knee OA. Specifically, MSCs obtained from fat tissue is called autologous 
adipose stromal cells (ADSCs) and is garnering attention as a treatment of the painful 
degenerative knee joint. Part of the enthusiasm behind use of ADSCs as a treatment is the 
potential abundance of cells that can be harvested from the lipoaspiration (harvested fat cells), 
the high concentration of MSCs within the fat harvest and the low morbidity associated with fat 
harvesting and subsequent injection. Lipogems is an innovative suction lipoplasty system that 
involves the harvesting, processing and injection of 'microfragmented, minimally manipulated' 
fat that is composed of MSCs. Lipogems has been clinically available since 2013 and was FDA 
approved for orthopedic surgery in 2016. 
At this institution, the senior authors (RJW; AP) have been performing ADSCs using Lipogems 
as an addition to knee arthroscopy since 2016. Since its FDA approval, the Lipogems suction 
lipoplasty technique has been proposed as a treatment option in the management of mild to 
moderate osteoarthritis. While initial ADSC studies with Lipogems for management of 
osteoarthritis have demonstrated promising results, the clinical outcomes (functional, patient 
reported and radiographic) of ADSC as an adjunct to knee arthroscopy in the management of 
symptomatic knee effusion in the setting of osteoarthritis with meniscal tear is unclear.  
The first aim of this study is to report the patient-reported outcomes (pain, function and quality 
of life) after ADSC + arthroscopy for the management of symptomatic knee swelling and 
inflammation (effusion synovitis) in patients with mild to moderate knee OA  with or 
without meniscal tear. We will do this by comparing the characteristics among patients above 
and below a minimal important clinical change (MIC) threshold of 8 points on the KOOS pain 
scale to determine any clinical predictors for failure among this patient population. 
The second aim is to report the clinical outcomes of ADSC and arthroscopy in this patient 
population. Clinical outcomes will include presence and severity of knee effusion as well as 
measured knee range of motion at 2 weeks, 6 weeks, 12 weeks, 6 months and 1 year. Clinical 
outcomes will also include adverse events related to ADSC + arthroscopy within 90 days of 
treatment. 
The third aim of the study is to report the radiographic outcomes of ADSC and arthroscopy in 
this patient population. To achieve this, baseline preoperative non-contrast MRI will be 
compared to repeat MRI at 6 months by a board-certified radiologist. 
The final aim will be to retain discarded lipoaspirate from all patients in order to create a 
repository of lipoaspirate specimens for future study. 

Patients who present to the senior authors (RJW, AP) clinic with clinical and radiographic 
findings consistent with early symptomatic degenerative knee OA with effusion synovitis who 
have failed conservative treatment and who would have otherwise been indicated for knee 
arthroscopy with ADSC based on the clinical judgement of the senior authors, are screened, and 
approached by research staff based on the inclusion and exclusion criteria outlined in the study 
protocol. 
Patients who meet criteria for the study will under knee arthroscopy with adjunct ADSC 
injection as routinely performed by the senior authors. Following the procedure, they will be 
followed at clinical intervals of 2 weeks, 6 weeks, 12 weeks, 6 months and 1 year to report 
clinical and radiographic outcomes of the procedure. Ultimately, 50 patients will be enrolled in 
this prospective observational study 
Hypotheses:  
• 
Hypothesis 1: 
o (a) We hypothesize that the majority of patients undergoing ADSC+ knee 
arthroscopy will meet the MIC of 8 points on the KOOS pain scale from baseline 
to 6 months. 
o (b) Patients undergoing ADSC + arthroscopy will also demonstrate improvements 
on the other 4 KOOS subscales: KOOS Symptoms, Function in daily living 
(KOOS ADL), Function in Sport and Recreation (KOOS Sport/Rec), and knee-
related Quality of Life (KOOS QOL). 
o (c) Patients undergoing ADSC + arthroscopy achieving the MIC on the KOOS 
pain scale will also demonstrate improvements on the IKDC score and the NRS 
pain subscale. 
o (d) Patients undergoing ADSC + arthroscopy achieving the MIC on the KOOS 
pain subscale will maintain it at 12 months. 
• 
Hypothesis 2:  
o Patients undergoing ADSC + arthroscopy will have clinical improvement of at 
least one effusion grade and no change in knee range of motion at all measured 
time points out to 1 year. 
• 
Hypothesis 3:  
o Repeat MRI will demonstrate measurable improvement in effusion/synovitis 
features from baseline. 
 
Trial Design:  
 
• 
Participants are screened and approached by research staff based on the inclusion and 
exclusion criteria outlined below. If patients are not found to meet the inclusion criteria 
for the intervention at the time of their diagnostic arthroscopy, they will not undergo 
suction lipectomy graft harvesting. Only patients who are eligible based on inclusion 
criteria will undergo the graft harvest. 
• 
Diagnostic Arthroscopy and Harvesting 

o A diagnostic arthroscopic examination of the knee is performed in all eligible 
patients using standard anterolateral and anteromedial portals and a 4-mm 
arthroscope. The treating surgeon will exam the medial, lateral, and 
patellofemoral joint compartments and grade the intra-articular pathologic 
changes. If the patient is confirmed to be eligible, then the surgeon will proceed 
with adipose graft harvesting from the abdomen using liposuction per standard 
protocol (see adipose harvest protocol below). After the Adipose Tissue 
Emulsification and Harvest portion of the protocol is completed, the surgeon 
proceeds with the remainder of the knee arthroscopy. 
o Any reactive synovitis is debrided. The knee is inspected for meniscal tears, 
loose bodies, chondral flaps, synovial plica and fat pad adhesions, which can 
be addressed surgically without excluding the patient from the 
study. Concomitant procedures that are allowed will include: chondroplasty, 
partial meniscectomy, plica excision, arthroscopic debridement including synovial 
debridement All therapeutic procedures are carefully documented and no invasive 
procedures beyond debridement of chondral flaps, meniscus or other soft tissue is 
allowed (such as microfracture, meniscal repair, ligament repair or 
reconstruction, osteotomy or other realignment procedures) . 
• 
Patient Positioning: 
o The patient is positioned supine. Prophylactic antibiotics are given intravenously 
prior to skin incision. The abdominal area and lower extremity are draped and 
then prepped using ChloraPrep. The entire abdomen from the xiphoid process to 
the pubiSterile 1015 U-drapes (Steri-Drape; 3M, St. Paul, MN) are placed just 
distal to the tourniquet and around the prepped area of the flanks and abdomen. 
Sterile split drapes are then used to drape the abdominal area free followed by an 
extremity drape. A rectangular area is cut in the extremity drape to expose the 
abdominal area. Four strips of 3M Ioban 2 Antimicrobial Drapes are used to seal 
the operative field along the perimeter of the cut-out section in the extremity 
drape 
• 
Adipose Tissue Emulsification and Harvesting: 
o The right flank area is injected with 1% lidocaine with epinephrine to create a 
small skin wheal. An 11-blade scalpel is used to make a stab incision in the 
subcutaneous tissue. The tumescent solution contains 25 mL of 2% lidocaine and 
0.5 mL epinephrine (1:1,000) in a 250-mL bag of normal saline. This solution is 
injected subcutaneously using a 18 gauge cannula. Sixty milliliters of solution are 
injected below the umbilicus and 60 mL above the umbilicus. Gentle agitation of 
the tissue using a hacking tapotement technique is completed followed by a 10-
minute resting period to allow for adequate emulsification. The adipose tissue is 
then harvested with the liposuction cannula connected to a 10-mL Vaclok syringe 
(Lipogems International, Milan, Italy). This syringe allows the plunger to lock, 
creating a negative pressure vacuum. Liposuction of abdominal fat is performed 
using brisk broad strokes until a total of 80 to 120 mL of aspirate is obtained 
depending on the patient’s body habitus. The adipose tissue from each of the 
Vaclok syringes is transferred to a single 60-mL syringe using a luer lock 
connector. Enough adipose tissue is collected to prepare a 15cc quantity of 
transplantable lipoaspirate. 

• 
Lipoaspirate Processing:  
o The processing cylinder (Lipogems) containing the 5 stainless steel marbles is 
connected to 2 hoses. The hose attached to the blue or orange size reduction filter 
is connected to a bag of normal saline. The gray size reduction filter on the 
opposite end of the cylinder is attached to a hose connected to a waste bag, which 
rests on the floor. The cylinder is then rotated so that the gray filter points 
upward. Both the blue/orange filter hose and waste hose are opened to allow the 
cylinder to fill with normal saline while holding it vertically and shaking 
intermittently to remove air bubbles. Both hoses are then clamped closed once the 
cylinder is filled completely. The 60- mL syringe containing the lipoaspirate is 
connected to the blue/orange filter. The adipose tissue is injected into the 
processing cylinder through the blue/orange filter with the clamp on the gray 
waste side open. With the blue/orange filter pointing up, both clamps are opened 
to allow for rinsing or elimination of blood and oily impurities into the waste bag. 
Once the fluid is transparent, the shaking process will begin. Both hoses are 
clamped closed, and the cylinder is shaken for 30 seconds to allow the action of 
the steel spheres to emulsify and microfracture the adipose tissue. This sequence 
is repeated, followed by a final wash. Two 10-mL luer lock syringes are 
connected to both sides of the chamber in order to allow removal of the stem cell 
product. The processing cylinder is flipped with the gray filter at the top. The 
blue/orange filter hose is opened. Through the syringe connected to the 
blue/orange filter a full 10 mL of saline is drawn. The blue/orange filter hose is 
closed. The cylinder is held vertically with the gray filter at eye level. Acting on 
the syringe connected to the blue/orange filter, the saline is pushed into the 
cylinder, thus forcing the stem cell product through the gray filter into the empty 
syringe connected on top. The top syringe containing the stem cells is removed 
and placed facing up to allow the cells to settle within the syringe and separate 
from the excess fluid. The cylinder is shaken slightly, and the process is repeated 
to continue retrieving the cells. This is performed until no more cells are yielded 
from th cylinder. The individual syringes that were left standing on the bac table 
are decanted, removing the excess fluid that has separate from the stem cells. The 
cells are then combined into one syringe using a white luer lock connector. The 
goal is to obtain 15 mL of final stem cell product of which, 10mL will be injected 
into the knee. 
o The knee is aspirated dry, and the anteromedial portal is closed. An 18-gauge 
needle is placed into the knee and intraarticular placement is confirmed with 
direct visualization. Following placement of the needle, the arthroscope is 
removed, and the anterolateral portal is closed. The lipoaspirate syringe is applied 
to the remaining needle and the contents (10mL) are injected into the knee. The 
knee and the abdominal donor sites are sterilely dressed in standard fashion. 
o The remaining 5 mL (of the original 15mL aliquot) will be sealed in a 5 mL 
syringe and given to the research assistant for storage. The stored 5mL syringe 
will be transported by the research assistant to the HSS core histopathology lab 
for storage within 1 hour of preparation. 
 

 
Primary Outcome:  
 
• Primary Outcome - Baseline, 2 weeks, 6 weeks, 12 weeks, 6 months and 12 months 
o Knee Injury and Osteoarthritis Outcome Score pain subscale 
• The minimal important clinical change (MIC) threshold on the 
KOOS pain scale is 8 points  
 
Secondary Outcome:  
• Secondary Outcomes - Baseline, 2 weeks, 6 weeks, 12 weeks, 6 months and 12 months 
• Patient-reported outcomes 
o KOOS subscales (0 -100 points per scale) 
o KOOS Symptoms 
o KOOS ADL - Function in daily living 
o KOOS Sport/Rec - Function in sport and recreation 
o KOS QOL - knee-related quality of life 
§ International Knee Documentation Committee subjective knee form 
(IKDC-SKF) (0 -100 points) 
§ Numerical Pain Rating Scale for pain in KNEE (0-10) 
§ Promis Global-10 
§ Marx Activity Rating Scale 
• Clinical Outcomes 
o Effusion grade based on stroke test effusion grading scale (Sturgill et al, JOSPT 
2009)  
o Knee ROM measure using goniometer  
• Adverse events: 
o Surgical site complications – knee effusion requiring therapeutic aspiration, 
surgical infection, knee stiffness requiring surgical manipulation 
o Donor site complications – persistent donor site pain, contour defects, permanent 
skin color changes, infection, embolism, hematomas, or seromas, persistent post-
operative bleeding. 
o Re-arthroscopy or knee replacement within 1 year of intervention. 
 
• Tertiary outcomes - Baseline, 6 months 
o The radiological efficacy of the procedure will be measured using the MRI OA 
Knee Score (MOAKS) criteria by a board certified radiologist to assess extent of 
effusion-synovitis as well cartilage damage using ICRS criteria on HSS-quality 
MRI scans, using fluid-sensitive sequences (such as intermediate-weighted 
sequences with and without fat suppression) and proton-density sequences. An 
MRI to assess ICRS grade will be performed at 6 months 
 
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