Adipose Stem Cell–Derived Exosomes Ameliorate Chronic Rotator Cuff Tendinopathy by Regulating Macrophage Polarization: From a Mouse Model to a Study in Human Tissue

作者：Chongyang Wang, Yao Zhang, Guangcheng Zhang, Weilin Yu, Yaohua He · 发表于：The American Journal of Sports Medicine · 年份：2021 · DOI：10.1177/03635465211020010 · 被引用次数：63 · 研究领域：Shoulder Injury and Treatment、Tendon Structure and Treatment、Sports injuries and prevention

Background: Chronic rotator cuff (RC) tendinopathy is one of the most prevalent causes of shoulder pain. Growing evidence suggests that macrophages play a significant role in the proinflammatory response, resolution of inflammation, and tissue healing of tendinopathy. In particular, enhancement of M2 macrophage (M2φ) activity contributes to the accelerated healing of tendinopathy. Therefore, a treatment that enhances M2φ polarization would be useful for patients with this common musculoskeletal disorder. Purpose: To investigate whether adipose stem cell–derived exosomes (ASC-Exos) enhance M2φ polarization and ameliorate chronic RC tendinopathy. Study Design: Controlled laboratory study. Methods: First, we compared the effects of ASC-Exos on polarization of mouse bone marrow–derived macrophages between a classically activated phenotype (M1φ) and an alternatively activated phenotype (M2φ) in vitro. In total, 72 C57BL/6 mice were assigned to normal cage activity (n = 24) or 5 weeks of treadmill overuse (n = 48). The supraspinatus tendon of each treadmill overuse mouse was treated with ASC-Exos (n = 24) or saline (n = 24). Histological and biomechanical outcomes were assessed 4 weeks after treatment. Finally, tissue samples from human patients with RC tendinopathy were obtained to assay the effect of ASC-Exos on the M1φ/M2φ balance in tissue-resident macrophages. Results: ASC-Exos inhibited M1φ polarization and augmented M2φ polarization in vitro and in vivo. Mice in the ASC-Exos...