Preclinical safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell medicinal product for rotator cuff repair: a two-phase experimental study.

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Cell therapy with adipose-derived mesenchymal stem cells (ASCs) is a promising biological augmentation strategy for rotator cuff repair; however, before clinical translation, regulatory frameworks mandate rigorous preclinical characterization of safety. We report the complete preclinical program evaluating both the safety of an allogeneic ASC-based cell therapy medicinal product (CTMP) and its efficacy in a chronic rotator cuff tear model. Methods Phase I (safety, 164 immunodeficient nude BALB/c mice) assessed toxicity, biodistribution, and tumorigenicity after intra-articular and intravenous administration at doses ranging from 10× to 1,000× the projected clinical dose. Toxicity was evaluated by biochemical panels and full-body histopathology at 90 days. Biodistribution was quantified by fluorodeoxyglucose-positron emission tomography/computed tomography (days 45 and 90) and human-specific quantitative polymerase chain reaction (Alu-repeat) at 90 days. Tumorigenicity used an HT-29 positive-control model. Phase II (efficacy, 48 Sprague-Dawley rats) used a validated 4-week chronic supraspinatus tear-and-repair model; after repair, animals received ASCs in suspension (n = 24) or Hypothermosol vehicle (n = 24) and were assessed histologically (Åström-Rausing scale) and biomechanically (Instron 4,411) at 4 months. Results In Phase I, no biochemical or histopathological t

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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