Therapeutic Effect of Genistein-Stimulated Human Mesenchymal Stem Cells in Myocardial Infarction

Stem cells offer significant therapeutic promise for the treatment of ischemic diseases. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy because of poor engraftment in vivo. Several strategies aimed at improving the survival and engraftment of stem cells in ischemic myocardium have been developed, including cell transplantation in combination with growth factor delivery, genetic modification of stem cells, and cell therapy by using scaffolds. In this study, we examined the effects of genistein on therapeutic efficacy in an acute myocardial ischemia model. We found that treatment with genistein induced enhanced human mesenchymal stem cell (hMSC) proliferation. These responses were accompanied by increases in the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 signaling. Blockade of each signal pathway abrogated the genistein-induced promotion of hMSC proliferation, suggesting that genistein affects both of these essential signaling pathways. Injection of genistein stimulate-hMSCs (geni + hMSCs) into myocardial ischemic sites in vivo induced cellular proliferation and survival of cells at the ischemic sites and thereby enhanced angiogenic cytokine secretion. These results show that genistein stimulate-hMSCs exhibits markedly enhanced anti-apoptotic capabilities compared to those exhibited by hMSCs alone; thus, they enhance the repair of ischemic myocardial injury through cell survival and angiogenic cytokine production.