Mechanism of Enhanced MerTK-Dependent Macrophage Efferocytosis by Extracellular Vesicles.

Objective: Extracellular vesicles secreted by cardiosphere-derived cells (CDC) polarize macrophages toward a distinctive phenotype with enhanced phagocytic capacity (M). These changes underlie cardioprotection by CDC and by the parent CDCs, notably attenuating the no-reflow phenomenon following myocardial infarction, but the mechanisms are unclear. Here, we tested the hypothesis that M are especially effective at scavenging debris from dying cells (ie, efferocytosis) to attenuate irreversible damage post-myocardial infarction.

Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning.

Background: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction by distinctive macrophage (Mϕ) polarization. Here we demonstrate that CDC-secreted exosomes (CDC) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning.

Methods: Rats and pigs underwent myocardial infarction induced by ischemia/reperfusion before intracoronary infusion of CDC, inert fibroblast exosomes (Fb; control), or vehicle.