Adipose stromal cells in the human rotator cuff are resistant to fibrotic microenvironmental cues

作者：Dakota R. Kamm, Akash Shaji, Kathryn L. Bohnert, Jay D. Keener, Amit Pathak, Gretchen A. Meyer · 发表于：The Journal of Physiology · 年份：2025 · DOI：10.1113/jp286563 · 被引用次数：4 · 研究领域：Shoulder Injury and Treatment、Sports injuries and prevention、Medical research and treatments

Rotator cuff tears are the most common upper extremity orthopaedic injury, causing degenerative changes within the bone, tendon, joint capsule, bursa and muscle. These degenerative changes are linked to poor rehabilitative and surgical outcomes, which has launched investigations into co-therapeutic biologics. Specifically, mesenchymal stem cells (MSCs) have shown promise in mitigating degenerative changes in animal models of rotator cuff tears, but reports of their impact on clinical outcomes remain mixed. Here we describe an alternative source of MSCs in the human shoulder, adipose stromal cells (ASCs) from the subacromial fat (SAF) pad. Compared to the gold-standard subcutaneous (SQ) fat, we show that SAF ASCs are less sensitive to chemical and mechanical fibrotic cues, (1) retaining smaller cell area with reduced actin stress fibre alignment across a range of physiological and pathological stiffnesses, (2) having reduced traction forces and extracellular matrix production, and (3) having reduced myofibroblastic conversion in response to cytokine challenge. Furthermore, we show that SAF ASCs enhance fusion of primary human myoblasts via paracrine signalling. Despite a fibrotic signature in SAF from rotator cuffs with tendon tears, SAF ASCs sourced from torn rotator cuffs were equally effective at resisting fibroblastic conversion and promoting myogenesis as those from intact rotator cuffs, further supporting autologous clinical use of these cells. In conclusion, this study ...