Exosomes derived from tendon stem/progenitor cells enhance tendon-bone interface healing after rotator cuff repair in a rat model
Bioactive Materials, vol. 40, pp. 484–502
Abstract
The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.
Authors 12
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Second Military Medical University · Shanghai Changzheng Hospital
Affiliation as printed
Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China
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Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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Southwest Medical University · Affiliated Hospital of Southwest Medical University
Affiliation as printed
Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
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Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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Second Military Medical University · Shanghai Changzheng Hospital
Affiliation as printed
Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China
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Shanghai Jiao Tong University · Shanghai First People's Hospital
Affiliation as printed
Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 200080, China
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Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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Zhiwen Luo corresponding
Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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Chen Xu corresponding
Second Military Medical University · Shanghai Changzheng Hospital
Affiliation as printed
Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China
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Shiyi Chen corresponding
Fudan University · Huashan Hospital
Affiliation as printed
Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China
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