Electrical Stimulation Increases the Maturity of Differentiated Cardiomyocytes and Improves Cardiac Function in Rats with Myocardial Infarction
ZHANG Lisha1, XIONG Tinglin1, YANG Yan2, ZHANG Xiaogang3*
This study explored the effect of electrical stimulation on the cardiac differentiation of induced pluripotent stem cells and evaluated the therapeutic effect of differentiated cardiomyocytes on myocardial infarction. Electrical stimulation and non-electric stimulation promoted induced pluripotent stem cells to differentiate into functional cardiomyocytes. qRT-PCR and cellular immunofluorescence were used to detect the expression levels of cardiogenic genes and functionally mature genes in differentiated cardiomyocytes. SD rats with myocardial infarction were established and randomly divided into myocardial infarction group, electrical stimulation group and control group, with 10 rats in each group. In the myocardial infarction group, only the coronary arteries were ligated. The electrical stimulation group and the control group were injected with differentiated cardiomyocytes pretreated with electrical stimulation and non-electrical stimulation at the border of myocardial infarction respectively. Echocardiography and invasive hemodynamics were used to detect cardiac function. Masson staining was used to evaluate the infarct area. Immunohistochemistry was used to detect the capillary density in the marginal area of infarction. The results showed that electrical stimulation could increase the spontaneous pulsation of differentiated cardiomyocytes, and up-regulate the expression of cardiogenic genes (Nkx2-5, GATA4, α-MHC and CX-43) and functionally mature genes(α-actinin and RYR2) of differentiated cardiomyocytes (P<0.05). The electrical stimulation significantly improved the cardiac function of rats with myocardial infarction, while reduced the infarct area and increased the capillary density in the marginal area of the infarction (P<0.05). The above results indicated that electrical stimulation could improve the efficiency of cardiac differentiation of induced pluripotent stem cells and promote the maturation of differentiated cardiomyocytes. Differentiated cardiomyocytes pretreated by electrical stimulation could significantly improve the cardiac function of rats with myocardial infarction.
CN
EN