Myocardial infarction (MI) is a major cause of death worldwide. Although percutaneous coronary intervention and coronary artery bypass grafting can prolong life, cardiac damage persists. In particular, cardiomyocytes have no regenerative capacity. Mesenchymal stem cells (MSCs) are attractive candidates for the treatment of MI. The manner by which MSCs exert a beneficial effect upon injured cells is a source of continued study. After the isolation and identification of exosomes from MSCs, the expression of miR-210 was determined by microarray chip. Subsequently, gain- and loss-function approaches were conducted to detect the role of exosomes and exosomal-miR-210 in cell proliferation and apoptosis of cardiomyocytes, as well as the MI in vivo. Dual-Luciferase Report Gene System was used to demonstrate the target gene of miR-210. We tested the hypothesis that MSC-derived exosomes transfer specific miRNA to protect cardiomyocytes from apoptotic cell death. Interestingly, direct cardiac injection of MSC exosomes reduced infarct size and improved heart function after coronary ligation. In vitro, the MSC exosomes enhanced cardiomyocyte survival to hypoxia. Confirmation of exosome uptake in myocytes was confirmed. Dual-luciferase reporter assay implicated miR-210 as a mediator of the therapeutic effect and AIFM3 as a downstream target. Treatment with miR-210 overexpressing MSC exosomes improved myocyte protection to both in vitro and in vivo stress. Furthermore, the endogenous and exogenous miR-210 had the same therapeutic effects. These results demonstrated that the beneficial effects offered by MSC-exosomes transplantation after MI are at least partially because of excreted exosome containing mainly miR-210.

中文翻译：

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缺氧挑战的 MSC 衍生的外泌体传递 miR-210 以减轻梗死后心脏细胞凋亡。

心肌梗塞 (MI) 是全世界死亡的主要原因。尽管经皮冠状动脉介入治疗和冠状动脉旁路移植术可以延长寿命，但心脏损伤仍然存在。特别是心肌细胞没有再生能力。间充质干细胞 (MSCs) 是治疗 MI 的有吸引力的候选者。MSCs 对受损细胞发挥有益作用的方式是继续研究的来源。从MSCs中分离鉴定外泌体后，通过微阵列芯片测定miR-210的表达。随后，进行了增益和损失函数方法以检测外泌体和外泌体-miR-210在心肌细胞增殖和凋亡以及体内MI中的作用。Dual-Luciferase Report Gene System用于证明miR-210的靶基因。我们检验了 MSC 衍生的外泌体转移特定 miRNA 以保护心肌细胞免于凋亡细胞死亡的假设。有趣的是，在冠状动脉结扎后，直接心脏注射 MSC 外泌体可减少梗塞面积并改善心脏功能。在体外，MSC 外泌体增强了心肌细胞对缺氧的存活率。确认了肌细胞中的外泌体摄取。双荧光素酶报告基因检测表明 miR-210 是治疗效果的介质，而 AIFM3 是下游靶标。用过表达 miR-210 的 MSC 外泌体处理改善了肌细胞对体外和体内应激的保护。此外，内源性和外源性miR-210具有相同的治疗效果。