Cardiomyocyte implantation has the potential to remuscularize the failing heart, offering a promising therapeutic approach. However, challenges such as ensuring adequate cardiomyocyte retention for long-lasting benefits while avoiding harmful side effects, including arrhythmias and tumor growth, remain. Recent study aimed to explore the hypothesis that epicardial engineered heart muscle (EHM) allografts, derived from induced pluripotent stem cell-based cardiomyocytes and stromal cells, can structurally and functionally restore the chronically failing heart in rhesus macaques, without causing adverse effects.

After confirming in vitro and in vivo (nude rat model) equivalence of a newly developed rhesus macaque EHM model to an established Good Manufacturing Practice (GMP)-compatible human EHM formulation, the researchers demonstrated that EHM grafts, consisting of 40 to 200 million cardiomyocytes/stromal cells, provided long-term retention (up to 6 months) and dose-dependent improvement in the target heart wall. Their results were consistent in macaques with or without myocardial infarction-induced heart failure. In the heart failure model, the EHM grafts enhanced heart wall contractility and ejection fraction, indicating support for both local and global heart function. Histopathological and gadolinium-based perfusion MRI analyses confirmed successful cell retention and vascularization.

No signs of arrhythmias or tumor growth were observed. These promising findings provide crucial evidence for the feasibility, safety, and efficacy of EHM grafts, laying the foundation for a first-in-human clinical trial on tissue-engineered heart repair. Subsequent clinical data confirmed successful remuscularization with EHM implantation in a patient with advanced heart failure.