MiRNA-Sequence Indicates That Mesenchymal Stem Cells and Exosomes Have Similar Mechanism to Enhance Cardiac Repair.

MiRNA-Sequence Indicates That Mesenchymal Stem Cells and Exosomes Have Similar Mechanism to Enhance Cardiac Repair.
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miRNA 序列表明间充质干细胞和外泌体具有相似的增强心脏修复的机制

DOI:
10.1155/2017/4150705
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发表时间:
2017
影响因子:
--
通讯作者:
Li Y
Li Y
中科院分区:
生物学3区
文献类型:
--
作者:
Shao L;Zhang Y;Lan B;Wang J;Zhang Z;Zhang L;Xiao P;Meng Q;Geng YJ;Yu XY;Li Y

文献摘要

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骨髓间充质干细胞(Mesenchymal stem cells,MSCs)通过旁分泌机制修复梗死心肌。我们试图比较MSC和MSC衍生的外泌体(MSC-Exo)在修复梗死心脏中的有效性,并确定MSC-Exo介导的心脏修复是如何调节的。在大鼠心肌梗死模型中,我们发现MSC-Exo可抑制心脏纤维化、炎症,并改善心功能。MSC-Exo的有益效果明显优于MSCs的上级。为了探索MSC-Exo作用的潜在机制,我们进行了几项体外实验和miRNA序列分析。MSC-Exo能促进H9 C2细胞增殖,抑制H2 O2诱导的细胞凋亡,抑制TGF-β诱导的成纤维细胞向肌成纤维细胞转化。重要的是,新的miRNA测序结果表明MSC-Exo和MSC具有相似的miRNA表达谱,这可能是MSC-Exo可以替代MSC进行心脏修复的原因之一。另外,MSC-Exo中几种miRNAs的表达与MSCs有显著差异,这可能解释了MSC-Exo治疗效果优于MSCs的原因。总之,本研究表明,MSC-Exo可以单独用于促进心脏修复,并且在修复受损心肌方面上级MSC。
Mesenchymal stem cells (MSCs) repair infarcted heart through paracrine mechanism. We sought to compare the effectiveness of MSCs and MSC-derived exosomes (MSC-Exo) in repairing infarcted hearts and to identify how MSC-Exo mediated cardiac repair is regulated. In a rat myocardial infarction model, we found that MSC-Exo inhibited cardiac fibrosis, inflammation, and improved cardiac function. The beneficial effects of MSC-Exo were significantly superior compared to that of MSCs. To explore the potential mechanisms underlying MSC-Exo's effects, we performed several in vitro experiments and miRNA-sequence analysis. MSC-Exo stimulated cardiomyocyte H9C2 cell proliferation, inhibited apoptosis induced by H2O2, and inhibited TGF-β induced transformation of fibroblast cell into myofibroblast. Importantly, novel miRNA sequencing results indicated that MSC-Exo and MSCs have similar miRNA expression profile, which could be one of the reasons that MSC-Exo can replace MSCs for cardiac repair. In addition, the expression of several miRNAs from MSC-Exo was significantly different from that of MSCs, which may explain why MSC-Exo has better therapeutic effect than MSCs. In conclusion, this study demonstrates that MSC-Exo could be used alone to promote cardiac repair and are superior to MSCs in repairing injured myocardium.