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

Background: Cellular 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. Methods: Animals modelling MI were randomly assigned to receive direct intramyocardial injection of culture medium (MI group) or 4 × 105 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 4 weeks post-MI. Invasive LV pressure measurement was measured at 4 weeks and was followed by sacrifice for histological examination. Results: Compared 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 4 weeks post-MI. Histological examination revealed a very limited number of iPS-CMs 4 weeks after transplantation. Nonetheless, there was a significant enhancement of angiogenesis and a reduction in apoptosis of native cardiomyocyte after iPS-CM transplantation. Conclusions: Our results demonstrate that transplantation of human iPS-CMs can improve heart function via paracrine action in a mouse model of myocardial infarction.