Extracellular vesicles derived from microRNA-150-5p-overexpressing mesenchymal stem cells protect rat hearts against ischemia/reperfusion.

ABSTRACT

An intriguing area of research has demonstrated the ability of extracellular vesicles (EVs) as biological vehicles for microRNAs (miRNAs) transfer. Mesenchymal stem cells (MSCs) produce large amounts of EVs. Rat models of ischemia/reperfusion (I/R) were established to explore the expression profile of thioredoxin-interacting protein (TXNIP), which was then knocked-down to investigate its effects on myocardial remodeling, followed by detection on myocardial infarction size (MIS), myocardial collagen volume fraction (CVF) and cardiomyocyte apoptosis. MSCs-derived EVs carrying miR-150-5p were cultured with neonatal cardiomyocytes under hypoxia/hypoglycemia condition for in vitro exploration and intramyocardially injected into I/R rats for in vivo exploration. I/R-induced rats presented higher TXNIP levels and lower miR-150-5p levels, along with increased cardiomyocyte apoptosis. miR-150-5p in MSCs was transferred through EVs to cardiomyocytes, leading to suppressed myocardial remodeling, as reflected by smaller MIS and CVF and suppressed cardiomyocyte apoptosis. I/R-treated rats injected with MSCs-derived EVs containing miR-150-5p showed a reduction in myocardial remodeling associated with the downregulation of TXNIP, which may be clinically applicable for treatment of I/R.