The functional recovery of ischemic human pluripotent stem cell-derived cardiomyocytes by secretome of heat shock-preconditioned umbilical cord mesenchymal stem cells

Background: Cardiovascular diseases are among most prevalent health problems all over the world as well as Iran. Particularly, myocardial infarction comprises 30% of death rate in the world, while 40% in Iran. Moreover, ischemic heart conditions can progress to heart failure. Chronic heart failure may result in serious conditions, making heart transplantation the only remaining clinical solution. However, there is limited number of organ donors which complicates this therapeutic option. Last two decades, cell therapy was introduced as a promising approach to tackle these situations. Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine due to their multipotency and paracrine effects. In this study, we aimed to compare the cardiac repair effects of MSCs’ secretome derived from three sources of adipose, bone marrow and umbilical cord in an in vitro model of hypoxia induced in human induced pluripotent stem cells (hiPSC)-derived cardiomyocytes. Methods: Hypoxia was induced in hiPSC-derived cardiomyocytes and neonatal mouse cardiomyocytes using 1 mM H2O2 for 4 hours. Hypoxia induction was confirmed by translocation of Hif-1α into nucleus as visualized by immunostaining of cells pre and post-hypoxia. The cardiomyocytes were then subjected to indirect co-culture with heat shock-preconditioned MSCs post hypoxia, in order to receive MSCs secretome. Findings: Electrophysiological evaluation of cardiomyocytes as well as their contraction analysis post-MSCs secretome reperfusion, showed that umbilical cord MSCs could superiorly recover excitation-contraction coupling in cardiomyocytes. Conclusion: In conclusion, umbilical cord MSCs might be the best MSCs source for cardiac cell therapy or its secretome as a cell free approach.