Poor survival after myocardial infarction in immune deficient NXG B2m mice is alleviated by transplantation of induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) formulated as spheres, but not single cells

The human heart lacks cardiac stem cells and the ability to reestablish the loss of ventricular cardiomyocytes (vCMs) after myocardial infarction (MI) resulting in heart dysfunction. vCM replacement using intracardiac transplantation of human induced pluripotent stem cell (iPSC) derived vCMs represent a promising strategy for targeting MI, but low engraftment remains a challenge. Herein, we investigated whether formulation of ventricular iPSC-CMs (iPSC-vCM) as spheres (iPSC-vCMSphere) improves cell retention and cardiac function as directly compared to single-cells (iPSC-vCMSC) after transplantation in a new severely immunocompromised mouse model with MI. Recipient survival immediately after MI and intervention was poor for both Vehicle (50%) and iPSC-vCMSC (36%) groups, whereas 92% of iPSC-vCMSphere treated mice survived, which is comparable to non-immune deficient C57bl/6 mice (91%). All surviving and engrafted animals retained iPSC-vCMs in the infarct border zone at 8-weeks, and heart function remained similar between groups, although minor improvements were observed for iPSC-vCMSphere animals. Surprisingly, iPSC-vCMSpheres were less mature than iPSC-vCMSCs. Thus, our data suggest that iPSC-vCM sphere formulation may offer some benefits for intracardiac delivery as compared with single cell formulated iPSC-vCMs, and thus remains a promising candidate for reestablishing the lost CMs after MI in the future.