Abstract
Background: 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.
Objectives: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: Myocardial infarction, stromal cell-derived factor 1α, CXCR4, stem cells, homing, bone marrow.
Graphical Abstract
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