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: 41 months follow-up of a prospective, randomized, controlled, first-in-human clinical trial

BackgroundSymptomatic, 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. MethodsSubjects 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 either a single injection of an average 11.4 x 106 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. As per protocol efficacy was assessed using the ASES Total score, RAND Short Form-36 Health Survey (SF-36) Total score and VAS pain score at 24 weeks (W24) and W52 post-treatment as well as at 33.2 {+/-} 1.0 (mean {+/-} standard deviation) months (M33) and 40.6 {+/-} 1.9 months (M41) post-treatment. Magnetic resonance imaging (MRI) of the index shoulder was performed at baseline, W24, W52, M33 and M41 post-treatment. ResultsThere were no greater risks connected with injection of UA-ADRCs than those connected with injection of corticosteroid. Injection of UA-ADRCs resulted in significantly higher mean ASES Total scores at W24, W52 and M41, a significantly higher mean SF-36 Total score at W24, and significantly higher mean VAS Pain scores at W24 and W52 post-treatment than injection of corticosteroid (p<0.05). Treatment outcome could not be assessed using measurements of tear volume on MRI scans. On the other hand, MRI scans at W24 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. ConclusionsThe present study further supports management of sPTRCT with injection of UA-ADRCs. Trial registrationClinicaltrials.gov NCT04077190 (September 4, 2019).