Exosomes derived from tendon stem/progenitor cells enhance tendon-bone interface healing after rotator cuff repair in a rat model  

作　　者：Yanwei He Shihao Lu Wenbo Chen Li Yang Fangqi Li Peng Zhou Zan Chen Renwen Wan Zifan Zhang Yaying Sun Jinrong Lin Yisheng Chen Zhiwen Luo Chen Xu Shiyi Chen 

机构地区：[1]Department of Sports Medicine,Huashan Hospital Fudan University,Shanghai,200040,China [2]Department of Orthopedics,Shanghai Changzheng Hospital,Naval Medical University,Shanghai,200003,China [3]Department of Rheumatology and Immunology,Affiliated Hospital,Southwest Medical University,Luzhou,Sichuan,646000,China [4]Department of Trauma and Reconstructive Surgery,RWTH Aachen University Hospital,Aachen,52074,Germany [5]Department of Orthopaedics,The Affiliated Hospital of Southwest Medical University,Luzhou,646000,China [6]Department of Sports Medicine,Shanghai General Hospital,Shanghai Jiaotong University,Shanghai,200080,China

出　　处：《Bioactive Materials》2024年第10期484-502,共19页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant No.82172511,81972125 and 82172510);Shenzhen“San-Ming”Project of Medicine(No.SZSM202211019).

摘　　要：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 cellfree 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.

关 键 词：Tendon stem cells EXOSOME Macrophages MicroRNA-21a-5p Rotator cuff tear Tendon-to-bone healing 

分 类 号：R686[医药卫生—骨科学]