Cardiac repair in a murine model of myocardial infarction with human induced pluripotent stem cell-derived cardiomyocytes

BackgroundCellular replacement strategies using human induced pluripotent stem cells (iPSCs) and their cardiac derivatives are emerging as novel treatments for post-myocardial infarction (MI) heart failure (HF); however, the mechanism of recovery of heart function is not very clear. The purpose of this study was to investigate the efficiency of using highly purified human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) for myocardial repair in a mouse model of MI and to clarify the mechanism of recovery of heart function.MethodsAnimals modelling MI were randomly assigned to receive direct intramyocardial injection of culture medium (MI group) or 4x10(5) iPS-CMs (cell group) at the infarct border zone. Left ventricle (LV) performance was assessed with serial cardiac electrophysiology and was measured 1, 2 and 4weeks post-MI. Invasive LV pressure measurement was measured at 4weeks and was followed by sacrifice for histological examination.ResultsCompared to the MI group, the left ventricle ejection fraction (LVEF), left ventricular internal diameter in end-diastole (LVIDd) and end-systole (LVIDs) and maximal positive and negative pressure derivative (dP/dt) were significantly improved in the iPS-CM group at 4weeks post-MI. Histological examination revealed a very limited number of iPS-CMs 4weeks after transplantation. Nonetheless, there was a significant enhancement of angiogenesis and a reduction in apoptosis of native cardiomyocyte after iPS-CM transplantation.Conclusions p id=Par Our results demonstrate that transplantation of human iPS-CMs can improve heart function via paracrine action in a mouse model of myocardial infarction.