Bone marrow mesenchymal stem cell-derived exosomes promote tendon regeneration by facilitating the proliferation and migration of endogenous tendon stem/progenitor cells
Bone marrow mesenchymal stem cell-derived exosomes promote tendon regeneration by facilitating the proliferation and migration of endogenous tendon stem/progenitor cells
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骨髓间充质干细胞来源的外泌体通过促进内源性肌腱干/祖细胞的增殖和迁移来促进肌腱再生
DOI：
10.1016/j.actbio.2020.01.051
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发表时间：
2020-04-01
影响因子：
9.7
通讯作者：
Ao, Yingfang
中科院分区：
文献类型：
--
作者：
Yu, Huilei;Cheng, Jin;Ao, Yingfang
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）来源的exosomes作为一种新型的生物促再生治疗剂正日益受到关注。在这里，我们探索了一种新的基于外泌体的治疗应用与局部纤维蛋白递送策略相结合用于肌腱修复的潜力。在发现骨髓间充质干细胞来源的exosomes（BMSCs-exos）在体外可促进肌腱干/祖细胞（TSPC）的增殖、迁移和向肌腱分化后，我们将BMSCs-exos包埋在纤维蛋白中，并注射到大鼠髌腱缺损区，结果表明，exosomes可从纤维蛋白中控制释放，滞留在缺损区，并被TSPC内化。包埋在纤维蛋白中的BMSCs-exos显著改善了组织学评分，增强了Mohawk，Tenomodulin和I型胶原的表达，以及新生肌腱的力学性能，并且还促进了局部TSPC的增殖。总之，我们证明了BMSCs-exos在肌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的成功局部治疗策略。这项研究为外泌体在肌腱损伤的新疗法中的潜在应用带来了前景。意义声明间充质干细胞已被确定为组织再生的首选方法。本研究报道了骨髓间充质干细胞（BMSCs）通过纳米外泌体的旁分泌信号作用促进肌腱干/祖细胞（TSPC）的增殖和迁移。我们还证明，BMSC来源的exosomes的应用可能是一种有前途的方法，激活内源性TSPC在肌腱损伤区域的再生潜力，纤维蛋白-exosomes递送系统代表了一种成功的exosomes局部治疗策略。(C)2020 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
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 SignificanceMesenchymal 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. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.