Institute of Sports Medicine, Beijing Key laboratory of Sports Injuries, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, P.R.China.
Institute of Sports Medicine, Beijing Key laboratory of Sports Injuries, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, P.R.China.
Acta Biomater. 2020 Apr 1;106:328-341. doi: 10.1016/j.actbio.2020.01.051. Epub 2020 Feb 4.
Mesenchymal stem cells (MSCs)-derived exosomes are being increasingly focused as the new biological pro-regenerative therapeutic agents for various types of tissue injury. Here, we explored the potential of a novel exosome-based therapeutic application combined with a local fibrin delivery strategy for tendon repair. After discovering that bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) promoted the proliferation, migration and tenogenic differentiation of tendon stem/progenitor cells (TSPCs) in vitro, we embedded BMSCs-exos in fibrin and injected it into the defect area of rat patellar tendon, and the results showed that the exosomes could be controlled-released from the fibrin, retained within the defect area, and internalized by TSPCs. BMSCs-exos embedded in fibrin significantly improved the histological scores, enhanced the expression of mohawk, tenomodulin, and type I collagen, as well as the mechanical properties of neotendon, and also promoted the proliferation of local TSPCs in vivo. Overall, we demonstrated the beneficial role of BMSCs-exos in tendon regeneration, and that fibrin-exosomes delivery system represents a successful local treatment strategy of exosomes. This study brings prospects in the potential application of exosomes in novel therapies for tendon injury. STATEMENT OF SIGNIFICANCE: Mesenchymal stem cells have been identified as a preferred approach in tissue regeneration. In this study, we reported bone marrow mesenchymal stem cells (BMSCs) promote the proliferation and migration of tendon stem/progenitor cells (TSPCs) via the paracrine signaling effect of the nanoscale exosomes. We also demonstrated that the application of BMSCs-derived exosomes might be a promising approach to activate the regenerative potential of endogenous TSPCs in tendon injured region, and fibrin-exosomes delivery system represents a successful local treatment strategy of exosomes.
间充质干细胞（MSCs）衍生的外泌体作为各种组织损伤的新型生物再生治疗剂越来越受到关注。在这里，我们探索了一种新型的外泌体治疗应用与局部纤维蛋白递药策略相结合用于腱修复的潜力。在发现骨髓间充质干细胞衍生的外泌体（BMSCs-exos）在体外促进肌腱干/祖细胞（TSPCs）的增殖、迁移和腱向分化后，我们将 BMSCs-exos 嵌入纤维蛋白中并注射到大鼠髌腱的缺损区域，结果表明外泌体可以从纤维蛋白中控制释放，保留在缺损区域内，并被 TSPCs 内化。纤维蛋白中嵌入的 BMSCs-exos 显著改善了组织学评分，增强了 mohawk、腱调蛋白和 I 型胶原的表达，以及新腱的机械性能，并且还促进了体内局部 TSPCs 的增殖。总的来说，我们证明了 BMSCs-exos 在腱再生中的有益作用，并且纤维蛋白-外泌体递送系统代表了外泌体局部治疗策略的成功。这项研究为外泌体在肌腱损伤的新型治疗中的潜在应用带来了前景。
