Cardiac Repair
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Because current treatments have been limited in reducing morbidity and mortality associated with heart failure, the transplantation of cells into the heart has emerged as a potential therapy to repair damaged myocardium and reverse end-stage heart failure. We have identified and isolated a novel population of skeletal muscle-derived stem cells (MDSCs) from mice and have investigated the potential of MDSC transplantation for cardiac repair. After intramyocardial transplantation of MDSCs into the hearts of dystrophin-deficient mdx mice, a model of cardiomyopathy and muscular dystrophy, we have observed that MDSCs generated large persistent grafts consisting primarily of numerous skeletal muscle myocytes with a substantially smaller number of donor-derived cardiomyocytes located primarily at the graft–host myocardium border. Employing a mouse model for acute myocardial infarction, we have reported that, in comparison with committed skeletal myoblast and control saline-injected hearts, MDSCs implanted into infarcted hearts elicited significant improvements in cardiac performance despite their inability to fully differentiate into cardiomyocytes. Further experiments based on gain- and loss-of-function of VEGF have demonstrated that MDSC transplantation elicits improvements in cardiac performance by inducing neovascularization of ischemic myocardium through the secretion of VEGF. Taken together, these results suggest that the implantation of MDSCs represents a promising cellular therapy to promote cardiac repair.
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