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

J Orthop Surg Res. 2020 Mar 30;15(1):122. doi: 10.1186/s13018-020-01631-8.

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 × 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 12 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. However, one subject in the corticosteroid group developed a full rotator cuff tear during the course of this pilot study. Despite the small number of subjects in this pilot study, those in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than those in the corticosteroid group (p < 0.05).

Discussion: This pilot study suggests that the use of UA-ADRCs in subjects with sPTRCT is safe and leads to improved shoulder function without adverse effects. To verify the results of this initial safety and feasibility pilot study in a larger patient population, a randomized controlled trial on 246 patients suffering from sPTRCT is currently ongoing.

Trial registration: Clinicaltrials.gov ID NCT02918136. Registered September 28, 2016, https://clinicaltrials.gov/ct2/show/NCT02918136.

Level of evidence: Level I; prospective, randomized, controlled trial.

Keywords: Adipose-derived regenerative cells (ADRCs); Partial rotator cuff tear; Point of care treatment; Safety; Shoulder disease; Stem cells; Stromal vascular fraction.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / physiology*
  • Adipose Tissue / transplantation*
  • Adult
  • Aged
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Point-of-Care Systems*
  • Prospective Studies
  • Regeneration / physiology*
  • Rotator Cuff Injuries / diagnostic imaging
  • Rotator Cuff Injuries / therapy*
  • Single-Blind Method
  • Stem Cell Transplantation / methods*
  • Transplantation, Autologous / methods
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT02918136