Intravenous administration of embryonic stem cells home into injured hearts and improve cardiac function post myocardial infarction in rats / 中华急诊医学杂志

ABSTRACT

Objective To clarify whether the intravenous administration of embryonic stem cells(ESCs)could home in on injured myocardium caused by acute myocardial infarction(MI)in rats and to improve the cardiac function afterwards,and to explore the possible effect of inflammatory factor TNF-?on it.Methods ESCs were cultured in vitro and transfected with green fluorescence protein(GFP).The model of heart failure post MI in rats was established by permanent ligation of left coronary anterior descend artery.After operation the rats were administered with 10~7 ESC via tail vein every other day for 6 days.The sham and MI without ESCs infusion groups served as control.Six weeks later,the hemodynamic measurement was employed to evaluate the cardiac function.Immunohistochemistry assay was used to detect the GFP expression in heart and other organs,and the cardiac specific protein Tropinin I(Tn I)expression in GFP positive spot of heart.Meanwhile,the co-culture in vitro of ESC and neonatal rat cardiomyocytes was used to observe the effect of overexpression of TNF-?in cardiomyocytes on ESC migration.Results Six weeks after MI,cardiac function was significantly improved in rats administered with ESC in comparison with those of MI group.Histological changes demonstrated that infused ESCs formed GFP-positive grafts in infracted myocardium.Alternatively,the positive immunostaining for Tn I was found in the area corresponding to GRP positive staining.In regard to other organs,only in spleen a few GFP positive cells were found.This would indicate that circulating ESC could translocate to infracted myocardium and to form cardiac tissue.Migration assay of ESC in vitro indicated that cultured cardiomyocytes with overexpression of TNF-aobviously enhanced the migration of ESCs in comparison with cardiomyocytes without transfection. Conclusion Intravenously infused ESC could home in on infarcted myocurdium and futher differentiate into cardiomyocytes which led to the improvement of cardiac function.In the setting of acute MI the homing mechanism Could be associated with locally released inflammatory factors such as TNF-?which may play as a chemotactic agent on circulating ESC.