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.
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).
