Safety and Efficacy of Treating Symptomatic, Partial-Thickness Rotator Cuff Tear with Fresh, Uncultured, Unmodified, Autologous Adipose Derived Regenerative Cells (UA-ADRCs) Isolated at Point of Care: A Prospective, Randomized, Controlled First-in-Human Pilot Study

Abstract

Background: This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tear (sPTRCT) with fresh, uncultured, unmodified, autologous adipose derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at point of care is safe and more effective than corticosteroid injection. Methods: Subjects aged between 30 and 75 years with sPTRCT who did not respond to traditional nonoperative care for at least six weeks were randomly assigned to receive a single injection of an average 11.4×106 UA-ADRCs (in 5 ml liquid; mean cell viability: 88%) (n=11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/ml; 2 ml) plus 3 ml of 0.25% bupivacaine (n=5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey and pain visual analogue scale (VAS) at baseline (BL) as well as 3 weeks (W3), W6, W9, W12, W24, W32, W40 and W52 post treatment. Fat-saturated T2 weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment. Results: No severe adverse events related to the injection of UA-ADRCs were observed in the twelve months post treatment. The risks connected with treatment of sPTRCT with UA-ADRCs were not greater than those connected with treatment of sPTRCT with corticosteroid injection. Subjects in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than subjects in the corticosteroid group (p < 0.05). Discussion: Injection of fresh, uncultured, unmodified, autologous adipose derived regenerative cells is a safe and effective treatment of sPTRCT. Larger trials are needed to verify this result. Trial registration: Clinicaltrials.gov ID NCT02918136. Registered September 28, 2016. Level of evidence: Level I; prospective, randomized, controlled trial.

Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine

“…In our recent reports about the application of uncultured, autologous, fresh, unmodified, adipose derived regenerative cells (UA-ADRCs) isolated at point of care (i.e. ; at the same intervention procedure between harvesting, processing of adipose tissue and injection of cells) with the Transpose RT /Matrase System (InGeneron, Houston, TX, USA), we applied these considerations [7][8][9]. As such, we define treatments with UA-ADRCs as follows:…”

“…They can be administered "On Site" into a patient's damaged tissue in need of regeneration (e.g. ; bone defects [7], heart tissue with impaired function as a consequence of previous myocardial infarction [8] or partial tendon ruptures [9], respectively) immediately after isolation of the cells (usually within less than two hours after harvesting of the adipose tissue). Cultivating UA-ADRCs (generating so called ASCs) comes along with possibly culture-related issues affecting their safety as a medicinal product [13].…”

“…Combined with a temporary blockage of the coronary vein at the level of a previous arterial occlusion, this allows application precisely into the cardiac tissue in need of regeneration [8]. In the case of partial tendon ruptures the cells can be directly injected into the damaged site of the tendon [9]. It is obvious that the latter applications require a final cell suspension of small volume, which is achieved with our technology (e.g.…”

“…It is obvious that the latter applications require a final cell suspension of small volume, which is achieved with our technology (e.g. ; 5 mL of ADRCs in [9]).…”

“…Finally, we do not apply any other treatment together with UA-ADRCs, except for adequate rehabilitation (such as optional outpatient rehabilitation with physical therapy modalities in case of tendon regeneration [9]).…”