Sánchez-Sánchez, RafaelGómez-Ferrer, MartaReinal-Ferre, IgnacioBuigues, MarcVillanueva-Bádenas, EstelaOntoria-Oviedo, ImeldaHernándiz, AmparoGonzález-King, HernánPeiró Molina, EstebanDorronsoro, AkaitzSepúlveda, Pilar2024-05-092024-05-092021-08-31https://riunet.upv.es/handle/10251/204071[EN] Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are an emerging alternative to cell-based therapies to treat many diseases. However, the complexity of producing homogeneous populations of EVs in sufficient amount hampers their clinical use. To address these limitations, we immortalized dental pulp-derived MSC using a human telomerase lentiviral vector and investigated the cardioprotective potential of a hypoxia-regulated EV-derived cargo microRNA, miR-4732-3p. We tested the compared the capacity of a synthetic miR-4732-3p mimic with EVs to confer protection to cardiomyocytes, fibroblasts and endothelial cells against oxygen-glucose deprivation (OGD). Results showed that OGD-induced cardiomyocytes treated with either EVs or miR-4732-3p showed prolonged spontaneous beating, lowered ROS levels, and less apoptosis. Transfection of the miR-4732-3p mimic was more effective than EVs in stimulating angiogenesis in vitro and in vivo and in reducing fibroblast differentiation upon transforming growth factor beta treatment. Finally, the miR-4732-3p mimic reduced scar tissue and preserved cardiac function when transplanted intramyocardially in infarcted nude rats. Overall, these results indicate that miR-4732-3p is regulated by hypoxia and exerts cardioprotective actions against ischemic insult, with potential application in cell-free-based therapeutic strategies.Reconocimiento (by)AngiogenesisCardiac function analysisExtracellular vesiclesFibrosisMesenchymal stromal (stem) cell (MSC)MiR-4732-3pMyocardial infarctionArtículo10.3389/fcell.2021.734143Abierto2296-634X34532322PMC8439391