Rapid Delivery of Hsa-miR-590-3p Using Targeted Exosomes to Treat Acute Myocardial Infarction Through Regulation of the Cell Cycle.

Acute myocardial infarction leads to heart failure due to inadequate regeneration of cardiomyocytes. Therefore, promotion of cardiomyocyte proliferation is the key for the restoration of cardiac function. Induction of the cell cycle and the downregulation of genes that inhibit cardiomyocyte proliferation could induce cardiomyocyte to re-enter into the proliferative state. Hsa-miR-590-3p has good application prospects in myocardial proliferation since it could downregulate the expression of genes inhibiting cell proliferation such as Hopx. However, delivering sufficient hsa-miR-590-3p to the infarct area with non-invasive and non-viral methods efficiently and rapidly is challenging. Based on the high expression of cTnl in the microenvironment of infarct area, we used gene transfection to express a cTnl-targeted short peptide on the surface of mesenchymal stem cells to obtain cTnl-targeted exosomes. These exosomes could localize to infarct area along a cTnl concentration gradient. Exosomes carrying hsa-miR-590-3p were endocytosis by cardiomyocytes and thus promoted cardiomyocyte proliferation in the peri-infarct area and eventually restored cardiac function. Our results show that targeted exosome is a minimally invasive, non-viral, efficient, and rapid delivery system for the treatment of acute myocardial infarction.