Abstract 150: Irisin Enhances Cardiac Progenitor Cell-induced Cardiac Repair in the Infarcted Heart

Abstract

Background: Our recent evidence has demonstrated that irisin, a newly identified cardiokine, is important for the development of cardiac protection. We and others have shown that engraftment of cardiac progenitor cells (CPCs) into infarcted hearts led to myocardium regeneration and neovascularization. The purpose of this study is aimed at investigating the functional role of irisin, a cardiokine, in facilitating engrafted Nkx2.5/CPCs to promote cardiac repair and preserve cardiac performance in infarcted hearts. Methods: Nkx2.5 CSCs were isolated from mouse embryonic stem cells and re-introduced into the infarcted myocardium in which the mouse MI model was created by permanent ligation of the left anterior descending artery. Nkx.2.5 CPCs were treated with or without irisin (5 ng/ml) for 24 hours to precondition CPCs. CPCs were transplanted into the infarcted heart through the pegylated fibrin delivery approach. Myocardial functions were evaluated by serial echocardiographic measurements. Histological analysis was employed to assess newly formed cardiogenesis and cardiac remodeling. Results: Eight weeks after engraftment, the retention of CPCs in the infarcted heart was increased significantly following pegylated fibrin delivery of CPCs as compared to the direct injection of cells. Engrafted CPCs demonstrated newly formed and proliferative cardiomyocyte structures, which was enhanced by treatment with irisin. Echocardiography showed improvements in ventricular function following the engraftment of CPCs, which was promoted by irisin in association with the attenuation of remodeling. Conclusion: Our results indicate that irisin-promoted, CPC-derived cardiac regeneration improves the restoration of cardiac function in infarcted hearts, suggesting that irisin holds promise in developing a potentially new therapeutic strategy in myocardial repair and suppressing remodeling.