Protective Effects of Rat Bone Marrow Mesenchymal Stem Cells-Derived Fusogenic Plasma Membrane Vesicles Containing VSVG Protein Mediated Mitochondrial Transfer on Myocardial Injury In Vitro

Abstract

Overexpression of spike glycoprotein G of vesicular stomatitis virus (VSVG) can induce the release of fusogenic plasma membrane vesicles (fPMVs), which can transport cytoplasmic, nuclear, and surface proteins directly to target cells. This study aimed to investigate the roles of rat bone marrow mesenchymal stem cells (rBMSCs)-derived fPMVs containing VSVG protein in myocardial injury and their related mechanisms. The plasmids of pLP-VSVG were used to transfect rBMSCs, and then fPMVs were obtained by mechanical extrusion. After that, H9c2 cells were first treated with hypoxia reoxygenation (HR) to establish a cardiomyocyte injury model, and then were treated with fPMVs to evaluate the rescue of rBMSCs-derived fPMVs on HR-induced cardiomyocyte injury. FPMVs containing VSVG protein were successfully prepared from rBMSCs with VSVG overexpression. Compared with control fPMVs, ACTB, HDAC1, VSVG, CD81, MTCO1, and TOMM20 were significantly up-regulated (p < 0.05), while eEF2 was significantly down-regulated (p < 0.05) in the fPMVs containing VSVG protein. Additionally, it was obvious fPMVs could carry mitochondria into H9c2 cells, and HR treatment significantly inhibited viability and induced apoptosis of H9c2 cells, as well as significantly increased the contents of TNF-α and IL-1β, and ROS levels both in cells and cellular mitochondria, while evidently reducing the levels of ATP, MRCC IV, and MT-ND1 (p < 0.05). However, fPVMs could remarkably reverse the changes in these indexes caused by HR (p < 0.05). RBMSCs-derived fPMVs containing VSVG protein may have protective effects on myocardial injury by mediating mitochondrial transfer and regulating mitochondrial functions.