Human PSC-Derived Cardiac Cells for Heart Failure: From Cell Therapy to Engineered Tissue Patches

Abstract Purpose of Review This comprehensive overview evaluates recent progress in human pluripotent stem cell-derived cardiomyocyte therapies to improve the outcome of heart failure patients, with emphasis on delivery routes, early clinical employment, and the barriers for sustained functional cardiac repair. Recent Findings Multiple complementary strategies for cardiac remuscularization are being pursued in parallel, including single cell suspension, multicellular spheroids, cardiomyocyte sheets, and engineered myocardial tissues. Early clinical translation has established feasibility across several platforms, while engineered heart muscle has provided the clearest evidence of persistent graft retention and structural myocardial augmentation. Cardiomyocyte sheets have reached conditional regulatory approval, and catheter-based spheroid delivery is entering clinical evaluation. However, arrhythmogenicity, immune rejection, incomplete maturation and manufacturing complexity remain major challenges on the path to the clinic. Summary Pluripotent stem cell-derived cardiac products are transitioning from experimental concepts to clinically tested therapies. Future progress will depend on identifying the optimal patient population, product format and delivery route, reducing the need for immunosuppression, and demonstrating meaningful improvements in patient hospitalization, quality of life, and survival.