Intravenous Injection of SDF-1α-overexpressing Bone Marrow Mesenchymal Stem Cells has a Potential Protective Effect on Myocardial Ischemia in Mice.

Abstract

Neutrophils are involved in the injury of myocytes during myocardial ischemia (MI). Stem cells migrate to the site of myocardial injury under homing signals and play a protective role, such as inhibiting inflammation. Chemokine SDF-1α and its related receptor CXCR4 are upregulated after myocardial infarction, which may play an important role in stem cell homing. This study aimed to explore the potential therapeutic effect of SDF-1α-modified bone marrow mesenchymal stem cells on myocardial ischemia/reperfusion (I/R) injury. We explored the role of SDF-1α modified bone marrow mesenchymal stem cells in vivo and in vitro. SDF-1α and CXCR4 expression was detected under hypoxia/reoxygenation (H/R) condition. Cell migration was detected by the transwell method. The levels of SDF-1α and IL-1β, IL-6, IL-10, and TNF-α were detected in different groups. In vitro, SDF-1α was mainly upregulated and secreted by cardiomyocytes, and cardiomyocytes recruited stem cells through the SDF-1/CXCR4 pathway to reduce the damage of polymorphic mononuclear neutrophils to cardiomyocytes under H/R. Upregulation of SDF-1α increased the migration ability of BMSC Stem Cells to H/R-induced cardiomyocytes. In vivo, intravenous injection of SDF-1α genemodified BMSC Stem Cells reduced inflammatory infiltration in the injured area as well as the level of systemic inflammatory factors. SDF-1α-overexpressing BMSC Stem Cells protected the heart function of mice and significantly reduced I/R-induced myocardial injury, which has a potential protective effect on MI.