Extracellular Vesicles From Endothelial Progenitor Cells Limit The Development Of Ventricular Dysfunction In A Mouse Model Of Myocardial Infarction

After myocardial infarction (MI), angiogenesis in the ischemic myocardium is essential for an optimal reparative process to limit the development of ventricular dysfunction. Cell-derived extracellular vehicles (EVs) are emerging as the next-generation strategy in tissue engineering. In this study, we aimed to determine the role of EVs derived from endothelial progenitor cells (EPC) in cardiac function post-MI. EVs were purified from the supernatant of EPC by density gradient centrifugation. MI was induced in C57BL/6 mice (n=23) by left coronary artery ligation and confirmed by EKG. Mice were randomized to receive purified EVs (n=10) or saline (n=10) in two zones of the myocardium, peri-ischemic and central ischemia zones, followed by weekly I.P. injection of EVs or saline for six weeks. Three mice underwent sham surgical procedures without coronary artery ligation. Cardiac magnetic resonance at the end of the follow-up showed significant impairment of left ventricle (LV) performance in the saline group, which was better preserved in mice treated with EVs (Fig 1) . Histological analysis in the LV showed increased collagen deposition in both MI groups (Fig 2A) . However, capillary density decreased more pronouncedly in the saline than in the EV group (Fig 2B) . Quantitative mRNA array revealed a differential relative mRNA expression in the EV group compared to saline (Fig 3) . The administration of EPC-derived EVs has a modest effect on preventing the development of LV adverse remodeling after ischemia, as it limits LV dilation at the long term in a mouse model of chronic MI.Funding: ISCIII (PI19/00264, SEC/FECINV- BAS 20/012)