Mitsugumin 53 improves myocardial ischemia-reperfusion injury by promoting iPSCs survival through regulating AnxA6...

Myocardial ischemia-reperfusion injury (MIRI) remains a significant challenge in cardiac therapy. Regenerative strategies like induced pluripotent stem cells (iPSCs) and protein-based therapies have shown promise in cardiac repair and regeneration. However, the specific mechanism remains largely unknown. In this study, iPSCs were successfully generated. The cells were characterized by the expression of Oct3/4⁺, Nanog⁺, Sox2^+, and SSEA-1⁺, as well as the adhesion molecules and growth factor receptors CD49e, CD29, CD105, CD117, and CD81, which are essential for stem cell activities. MG53 mitigated hypoxia/reoxygenation (H/R)-induced membrane damage and cell death in iPSCs by accumulating at injury sites and preserving membrane integrity. In vivo experiments further revealed that MG53 treatment significantly enhanced the survival and functional integration of iPSCs in myocardial tissue post-MIRI injury. The treatment led to a notable reduction in apoptosis and an increase in the regenerative capacity of the myocardium. Mechanistically, MG53 was found to bind AnxA6, with AnxA6 overexpression abolishing MG53's cytoprotective effects. In conclusion, our study suggested that MG53 may stabilize damaged membranes and enhance the survival and functional integration of iPSCs in myocardial repair through AnxA6 modulation. MG53-treated iPSCs may serve as a potent therapeutic strategy for myocardial repair post-MIRI injury.