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 (CDCexo) 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 CDCexo, inert fibroblast exosomes (Fbexo; control), or vehicle. Two days later, infarct size was quantified. Macrophages were isolated from cardiac tissue or bone marrow for downstream analyses. RNA sequencing was used to determine exosome content and alterations in gene expression profiles in Mϕ. Results:Administration of CDCexo but not Fbexo after reperfusion reduces infarct size in rat and pig models of myocardial infarction. Furthermore, CDCexo reduce the number of CD68+ Mϕ within infarcted tissue and modify the polarization state of Mϕ so as to mimic that induced by CDCs. CDCexo are enriched in ...