Human induced pluripotent stem cell-derived cardiomyocyte patches ameliorate right ventricular function in a rat pressure-overloaded right ventricle model.

Abstract

Right ventricular (RV) failure following surgical repair of congenital heart disease affects survival. Human induced pluripotent stem cell-derived cardiomyocyte (hiPS-CM) sheet transplantation ameliorated left ventricular dysfunction in preclinical studies, indicating its efficacy in RV failure in congenital heart disease. This study aimed to evaluate whether hiPS-CMs could improve RV function in rats with pressure-overloaded RV failure. F344/NJcl-rnu/rnu rats underwent pulmonary artery banding (PAB) via left thoracotomy. Four weeks after PAB, hiPS-CM patch transplantation to the RV was performed in the hiPS-CM group (n = 33), and a sham operation was performed in the sham group (n = 18). We evaluated cardiac catheterization, positron emission tomography data, and pathological results 8 weeks following PAB. RV end-diastolic pressure, the time constant of isovolumic relaxation, and end-diastolic pressure-volume relation were significantly ameliorated in the hiPS-CM group compared with in the sham group. Picrosirius red staining revealed that anti-fibrotic effects were significantly higher in the hiPS-CM group than in the sham group. Von Willebrand factor staining revealed significantly higher myocardial capillary vascular density in the hiPS-CM group than in the sham group. hiPS-CMs were detected in the epicardium 4 weeks after hiPS-CM sheet transplantation. The angiogenic gene expression in the myocardium was significantly higher in the hiPS-CM group than in the sham group. Overall, in rats with pressure-overloaded RV failure, hiPS-CM patch transplantation could improve diastolic function, suppress ventricular fibrosis, and increase capillary density, suggesting that it is a promising treatment for RV failure.