Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a
Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a
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DOI：
10.1242/jcs.170373
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发表时间：
2016-06-01
影响因子：
4
通讯作者：
Zhao, Robert Chunhua
中科院分区：
文献类型：
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作者：
Liang, Xiaolei;Zhang, Lina;Zhao, Robert Chunhua
血管生成在包括伤口愈合和组织修复在内的各种生理过程中起着至关重要的作用。它需要内皮细胞与其周围环境之间的紧密相互作用。间充质干细胞（MSC）是存在于血管周围环境中的非内皮细胞类型之一，已显示分泌外泌体以调节MSC与其靶细胞之间的细胞间通讯。在这项研究中，我们首先分离了人脂肪来源的MSC分泌的外泌体（adMSC-Exo），并研究了它们在血管生成中的作用。我们发现adMSC-Exo可以被内皮细胞摄取，并在体外和体内显著促进血管生成。进一步的研究表明，miR-125 a在adMSC-Exo中富集，并通过靶向其3'非翻译区抑制血管生成抑制因子DLL 4的表达。此外，adMSC-Exo及其外泌体转染的miR-125 a可抑制DLL 4的表达，通过促进内皮尖端细胞的形成来调节内皮细胞的血管生成。总之，我们的研究表明，adMSC-Exo可以将miR-125 a转移到内皮细胞，并通过抑制DLL 4促进血管生成。adMSC-Exo作为一种促血管生成因子，可能是治疗性组织修复的一个有希望的候选者。
Angiogenesis plays crucial roles in various physiological processes including wound healing and tissue repair. It requires a tight interaction between endothelial cells and their surrounding environment. Mesenchymal stem cells (MSCs), one of the non-endothelial cell types present in the perivascular environment, have been shown to secret exosomes to modulate intercellular communications between MSCs and their target cells. In this study, we initially isolated exosomes secreted by human adipose-derived MSCs (adMSC-Exo) and examined their roles in angiogenesis. We found that adMSC-Exo could be taken up by endothelial cells and significantly promote angiogenesis in vitro and in vivo. Further study showed that miR-125a was enriched in adMSC-Exo, and repressed the expression of the angiogenic inhibitor delta-like 4 (DLL4) by targeting its 3' untranslated region. Additionally, adMSC-Exo and its exosomal transferred miR-125a could repress DLL4 expression and modulate endothelial cell angiogenesis through promoting formation of endothelial tip cells. In conclusion, our study indicates that adMSC-Exo can transfer miR-125a to endothelial cells and promote angiogenesis by repressing DLL4. adMSC-Exo, as a pro-angiogenic factor, might be a promising candidate for therapeutical tissue repair.