Long-term safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells isolated at the point of care: 40 months follow-up of a prospective, randomized, controlled, first-in-human clinical trial

Objective: Symptomatic, partial-thickness rotator cuff tears (sPTRCT) are problematic. Management of sPTRCT with fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and leads to improved shoulder function without adverse effects. This study tested the hypothesis that management of sPTRCT with injection of UA-ADRCs is safe and more effective than injection of corticosteroid even in the long run. Methods: Subjects who had completed a former randomized controlled trial were enrolled in the present study. At baseline these subjects had not responded to physical therapy treatments for at least six weeks, and were randomly assigned to receive respectively a single injection of an average 11.4 x 10^6 UA-ADRCs (n = 11) or a single injection of 80 mg of methylprednisolone (n = 5). Safety was assessed by rigorously documenting and evaluating treatment emergent adverse events. Efficacy was assessed using the ASES Total score, pain visual analogue scale (VAS) and RAND Short Form-36 Health Survey at 33.2 {+/-} 1.0 (mean {+/-} standard deviation) and 40.6 {+/-} 1.9 months post-treatment. Proton density, fat-saturated, T2-weighted (PD FS T2), magnetic resonance imaging (MRI) of the index shoulder was performed at both study visits. Results: There were no greater risks connected with injection of UA-ADRCs than those connected with injection of corticosteroid. The subjects in the UA-ADRCs group showed statistically significantly higher mean ASES Total scores than the subjects in the corticosteroid group. Treatment outcome could not be assessed using measurements of tear volume on MRI scans. On the other hand, PD FS T2 MRI scans at six months post-treatment allowed to "watch the UA-ADRCs at work". There was no relationship between treatment outcome and baseline data, including those data characterizing UA-ADRCs that can be collected with a clinical test. Conclusions: The present study further supports treatment of sPTRCT with injection of UA-ADRCs. Trial registration: Clinicaltrials.gov NCT04077190 (September 4, 2019).