Abstract
Although stem cell-mediated treatment of ischemic diseases offers significant therapeutic promise, the limitation in the therapeutic efficacy of transplanted stem cells in vivo because of poor engraftment remains a challenge. Several strategies aimed at improving survival and engraftment of stem cells in the ischemic myocardium have been developed, such as cell transplantation in combination with growth factor delivery, genetic modification of stem cells, and/or cell therapy using scaffolds. To improve therapeutic efficacy, we investigated the effects of genistein on the engraftment of transplanted ECFCs in an acute myocardial ischemia model. Results: We found that genistein treatment enhanced ECFCs' migration and proliferation, which was accompanied by increases in the expression of ILK, α-parvin, F-actin, and phospholylation of ERK 1/2 signaling. Transplantation of genistein-stimulates ECFCs (GS-ECFCs) into myocardial ischemic sites in vivo induced cellular proliferation and secretion of angiogenic cytokines at the ischemic sites and thereby enhanced neovascularization and decreased myocardial fibrosis as well as improved cardiac function, as shown by echocardiography. Taken together, these data suggest that pretreatment of ECFCs with genistein prior to transplantation can improve the regenerative potential in ischemic tissues, providing a novel strategy in adult stem cell therapy for ischemic diseases.
Highlights
Several studies have recently reported promising results by modifying and enhancing stem cell-mediated ischemic myocardial repair and regeneration [1,2,3,4,5,6]
These results suggest that genistein may enhance migration and promote proliferation in endothelial colonyforming cells (ECFCs) at low concentrations, which were reduced at high concentrations
Several repair mechanisms are thought to involve circulating ECFCs mobilized from the bone marrow to sites of ischemic injury
Summary
Several studies have recently reported promising results by modifying and enhancing stem cell-mediated ischemic myocardial repair and regeneration [1,2,3,4,5,6]. Increasing evidence from experimental ischemic animal models suggests that endothelial progenitor cells (EPCs) participate in the process of neovascularization and tissue repair, leading to enhanced recovery of the ischemic myocardium [7,8,9,10]. The adverse effects of ischemic tissue on the survival and function of the transplanted ECFC during angio/vasculogenesis and tissue repair is still a poses a challenge and research on the means to enhance stem cell survival and function is limited. We propose new method of augmenting neovascularization by overcoming the poor engraftment of ECFCs into ischemic tissue and enhancing its ECFCs survival
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