Combination of IGF-1 gene manipulation and 5-AZA treatment promotes differentiation of mesenchymal stem cells into cardiomyocyte-like cells

Abstract

Mesenchymal stem cell (MSC) transplantation has been proposed as a promising therapeutic strategy for ischemic myocardium repair following myocardial infarction. Differentiation of MSCs into cardiomyocytelike cells prior to cell transplantation is advantageous in improving their potential clinical benefits for cardiac repair. In the present study, we isolated and cultured porcine MSCs and evaluated the synergistic effect of 5azacytidine (5AZA) treatment and insulinlike growth factor1 (IGF1) gene manipulation on MSC differentiation into cardiomyocytelike cells. Our results demonstrated that 5AZA treatment alone induced a limited cardiomyocytelike differentiation effect in vitro. Overexpression of the IGF1 gene in MSCs improved the induction effect of 5AZA, while knockdown of the IGF1 gene attenuated the differentiation. These results suggest that IGF1 is a significant stimulus affecting the cardiomyocytelike differentiation of porcine MSCs. In addition, the combination of IGF1 gene manipulation and 5AZA treatment provides a new strategy to obtain more committed differentiated cardiomyocytelike cells from porcine MSCs prior to cell transplantation.