Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction

Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 107NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9–14/group) at 4 days after 60-min coronary artery occlusion-reperfusion. Cardiac function and left ventricular remodeling were similarly improved in both iPSC-CM-treated groups. To mimic the ischemic environment in the infarcted heart, both cultured NHP and human iPSC-CMs underwent 24-hr hypoxia in vitro. Both cells and media were collected, and similarities in transcriptomic as well as metabolomic profiles were noted between both groups. In conclusion, both NHP and human iPSC-CMs confer similar cardioprotection in a rodent myocardial infarction model through relatively similar mechanisms via promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis. In this article, Wu and colleagues demonstrate the therapeutic similarities of non-human primate iPSC-CMs and human iPSC-CMs to treat myocardial infarction by improving cardiac function and attenuating myocardial remodeling in a rodent myocardial infarction model. Mechanisms of iPSC-CM therapy include promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis.