Exosomes derived from mir-214-3p overexpressing mesenchymal stem cells promote myocardial repair
Wenwu Zhu, Qingjie Wang, Jian Zhang, Ling Sun, Xiu Hong, Wei Du, Rui Duan, Jianguang Jiang, Yuan Ji, Haoran Wang, Bing Han
Abstract
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-214 OE -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-214 OE -Exo treatment were explored using western blot analysis and luciferase assay. Results in vitro , miR-214 OE -Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214 OE -Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214 OE -Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214 OE -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