DOI: 10.1161/jaha.126.050981 ISSN: 2047-9980

Stem Cell‐Derived Cardiac and Conduction System Cells for Heart Regeneration and Repair: Current Progress and Future Directions

Berra Koskulu, Tabish Ali, Ilkin Tetik‐Altintop, Cleva Villanueva, Maja Gomola, Bradley K. McConnell
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Cardiovascular disease remains the leading cause of global mortality, in part because the heart has limited regenerative capacity. Human‐induced pluripotent stem cells (hiPSCs) offer a scalable, patient‐specific platform for modeling heart disease, advancing drug discovery, and developing regenerative therapies. This review evaluates recent developments in hiPSC technology, beginning with the generation of patient‐specific models of inherited arrhythmias and cardiomyopathies. We examine progress in directing hiPSCs into specialized lineages, including cardiomyocytes, pacemaker cells, and Purkinje fibers, by highlighting key developmental signaling pathways and transcriptional regulators. Furthermore, we discuss emerging strategies for cell and therapeutic delivery, such as bioengineered patches and hydrogels, and address key challenges in cell maturation and functional integration. Finally, we review current clinical trials assessing the safety of hiPSC‐based treatments for heart failure and conduction disorders. These advancements underscore the dual potential of hiPSCs as essential research tools and as aspirational therapeutic resources.

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