Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the 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 tears (sPTRCT) with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the 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 physical therapy treatments for at least 6 weeks were randomly assigned to receive a single injection of an average 11.4 × 10 6 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.

Human Tendon Repair Following Injection of Autologous, Unmodified Stem Cells: A Comprehensive Immunohistochemical Evaluation

“…It further was not the aim of the present study to establish a clinical treatment. To more conclusively evaluate clinical results with UA-ADRCs for incomplete tendon tears, a respective pivotal RCT is now recruiting (Hurd, 2018) based on encouraging clinical results of the pilot study (Hurd et al, 2020). In summary, the results of this study indicate, for the first time, that treatment of an injured human tendon with unmodified, autologous regenerative cells can enable true regenerative healing.…”

“…As part of this process, approximately 100 g of abdominal adipose tissue was harvested by liposuction, from which approximately 75×10 6 UA-ADRCs were isolated within less than two hours using the Transpose RT system (InGeneron, Houston, TX, USA). Detailed characterizations of cells isolated from human adipose tissue using the Transpose RT system are available in the literature (Winnier et al, 2019;Hurd et al, 2020). The UA-ADRCs were injected into the injured supraspinatus tendon immediately after isolation.…”

“…A recent in vitro study demonstrated that fresh UA-ADRCs may be superior to cultured adipose derived stem cells (ASCs) as trophic mediators for tendon healing (Polly et al, 2019). In addition, we recently published the first-in-human pilot RCT on treating sPTRCT with UA-ADRCs (Hurd et al, 2020). In the latter study subjects treated with UA-ADRCs showed significant clinical improvement compared to subjects treated with corticosteroid injection (p < 0.05) at six and twelve months post treatment (Hurd et al, 2020).…”

“…In addition, we recently published the first-in-human pilot RCT on treating sPTRCT with UA-ADRCs (Hurd et al, 2020). In the latter study subjects treated with UA-ADRCs showed significant clinical improvement compared to subjects treated with corticosteroid injection (p < 0.05) at six and twelve months post treatment (Hurd et al, 2020).…”

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

“…Human clinical trials involving stem/progenitor cells for the treatment of musculoskeletal injuries are increasing [25][26][27][28][29]. Many of these trials involve somatic (adult) stem cells, with mesenchymal stem/progenitor cells being the most commonly used variety.…”