Electrical coupling between transplanted cardiomyocytes and host myocardium to prevent arrhythmia

Transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes offers new opportunities for myocardial repair after infarction. However, as demonstrated in large-animal model studies, such therapy also brings translational challenges, including arrhythmias arising from abnormal spontaneous beating of the engrafted cells or irregular conduction due to poor electrical coupling between host and transplanted tissue. Addressing these issues will have important implications for improving the safety and efficacy of regenerative therapies. This Review summarizes the fundamental mechanisms governing cardiac electrical activity and highlights recent technological advancements for triggering and imaging myocardial electrical function. We focus on emerging experimental platforms that overcome limitations of traditional whole-heart mapping approaches, including organotypic myocardial tissue slices combined with high-resolution optical mapping and optogenetic stimulation. We further discuss recent technological and biological developments in the field of cell transplantation for cardiac repair and examine strategies to manage post-transplant arrhythmia risk, with a particular focus on enhancing graft maturation and electrical integration to accelerate the safe and effective clinical translation of cardiac cell therapies. Finally, we describe recent clinical trials involving transplantation of hiPSC-derived cells into damaged hearts.