Let-7b-mediated pro-survival of transplanted mesenchymal stem cells for cardiac regeneration.
Let-7b-mediated pro-survival of transplanted mesenchymal stem cells for cardiac regeneration.
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DOI：
10.1186/s13287-015-0221-z
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发表时间：
2015-11-05
影响因子：
7.5
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Cheng J;Zhang P;Jiang H
基于干细胞的修复和再生用于心肌损伤后的心脏再生仍然是未满足的挑战，主要是由于移植在受体部位的细胞的低活力。越来越多的证据表明，局部存在的活性氧（ROS）通过细胞凋亡和自噬引起移植细胞死亡。Ham及其同事已经确定let-7 b是通过直接靶向caspase-3诱导间充质干细胞（MSC）凋亡和自噬的主要介质之一。重要的是，心肌内注射let-7 b修饰的MSC显著增强心室功能，并通过保护移植细胞免于凋亡和自噬促进大鼠心脏缺血再灌注模型中的心肌修复。这些发现为microRNA在体内递送后干细胞存活的作用提供了新的见解，并进一步证明microRNA修饰的MSC移植可能是组织修复和再生的有效治疗方法。
Stem cell-based repair and regeneration for cardiac regeneration following myocardial injury remain unmet challenges largely due to low viability of cells transplanted in the recipient sites. Accumulating evidence has revealed that local existence of reactive oxygen species (ROS) causes transplanted cell death via both apoptosis and autophagy. Ham and colleagues have identified let-7b as one of the primary mediators for ROS-induced apoptosis and autophagy of mesenchymal stem cells (MSCs) through direct targeting of caspase-3. Importantly, intramyocardial injection of let-7b-modified MSCs significantly enhanced ventricular function and facilitated myocardial repair by protecting transplanted cells from apoptosis and autophagy in the rat cardiac ischemia-reperfusion model. These findings provide novel insights into the roles of microRNA underlying stem cell survival following in vivo delivery, and offer further evidence that microRNA-modified MSC transplantation might be an effective therapeutic approach for tissue repair and regeneration.