Let-7b-mediated pro-survival of transplanted mesenchymal stem cells for cardiac regeneration

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.