Exosomes derived from mir-214-3p overexpressing mesenchymal stem cells promote myocardial repair

Abstract

Aims: Exosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms. Methods: Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214OE-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214OE-Exo treatment were explored using western blot analysis and luciferase assay. Results in vitro: , miR-214OE-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214OE-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214OE-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214OE-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway. Conclusion: Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function. Graphical abstract: [Figure not available: see fulltext.].