PDF(Pubmed)
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.
摘要：
手术修复后的再撕裂率仍然很高。间充质干细胞(MSCs)已广泛应用于再生医学几十年。然而,安全性和伦理问题限制了它们的临床应用。肌腱干/祖细胞（TSPC）衍生的外泌体已成为有前途的无细胞治疗剂。因此,迫切需要研究TSPC-Exos是否能促进腱-骨愈合,并阐明其潜在机制.在这项研究中,发现TSPC-Exos促进了扩散，迁移,和BMSCs中纤维发生标志物的表达。此外，TSPC-Exos表现出抑制M1巨噬细胞极化同时促进M2巨噬细胞极化的能力。在大鼠肩袖修复模型中,TSPC-Exos调节炎症并改善肌腱-骨界面的组织学结构，修复肌腱的生物力学特性，以及关节的功能。机械上,TSPC-Exos高表达miR-21a-5p,调节PDCD4的表达。PDCD4/AKT/mTOR轴与TSPC-Exos对增殖的治疗作用有关，迁移,和BMSCs的纤维发生。这项研究介绍了一种利用TSPC-Exos疗法作为无细胞疗法的有希望的策略的新方法。未来肩袖撕裂患者可能会受益。
