Journal
AMERICAN JOURNAL OF SPORTS MEDICINE
Volume 49, Issue 9, Pages 2321-2331Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/03635465211020010
Keywords
rotator cuff tendinopathy; adipose stem cell-derived exosomes; inflammation; macrophage
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The study showed that adipose stem cell-derived exosomes (ASC-Exos) inhibited M1 phi polarization and augmented M2 phi polarization, leading to improvement in chronic RC tendinopathy. Mice treated with ASC-Exos exhibited less severe pathological changes, higher maximum failure load, and stiffness compared to the saline group, suggesting that ASC-Exos could be a potential treatment for chronic RC tendinopathy by regulating the M1 phi/M2 phi balance.
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 (M2 phi) activity contributes to the accelerated healing of tendinopathy. Therefore, a treatment that enhances M2 phi polarization would be useful for patients with this common musculoskeletal disorder. Purpose: To investigate whether adipose stem cell-derived exosomes (ASC-Exos) enhance M2 phi 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 (M1 phi) and an alternatively activated phenotype (M2 phi) 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 M1 phi/M2 phi balance in tissue-resident macrophages. Results: ASC-Exos inhibited M1 phi polarization and augmented M2 phi polarization in vitro and in vivo. Mice in the ASC-Exos group showed less severe pathological changes than those in the saline group, including less cellular infiltration, disorganization of collagen, and ground substance deposition. The modified Bonar score of the ASC-Exos group (mean +/- SD, 7.68 +/- 1.03) was significantly lower than that of the saline group (9.81 +/- 0.96; P < .05). Furthermore, the maximum failure load was significantly higher in the ASC-Exos group than in the saline group (4.23 +/- 0.66 N vs 3.86 +/- 0.65 N; P < .05), as was stiffness (3.38 +/- 0.34 N/m vs 2.68 +/- 0.49 N/m; P < .05). Conclusion: ASC-Exos-mediated polarization balance of M1 phi/M2 phi contributes to the amelioration of chronic RC tendinopathy. Regulation of the M1 phi/M2 phi balance could be a new target for the treatment of chronic RC tendinopathy.
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