2014 June 12; 510(7504): 273–277. doi:10.1038/nature13233. | James J.H. Chong, Xiulan Yang, Creighton W. Don, Elina Minami, Yen-Wen Liu, Jill J Weyers, William M. Mahoney Jr., Benjamin Van Biber, Savannah M. Cook, Nathan J Palpant, Jay Gantz, James A. Fugate, Veronica Muskeli, G. Michael Gough, Keith W. Vogel, Cliff A. Astley, Charlotte E. Hotchkiss, Audrey Baldessari, Lil Pabon, Hans Reinecke, Edward A. Gill, Veronica Nelson, Hans-Peter Kiem, Michael A. Laflamme, and Charles E. Murry
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were shown to regenerate non-human primate hearts in a study led by James J.H. Chong and colleagues. The research demonstrated that hESC-CMs could be produced at a clinical scale (>1 billion cells per batch) and cryopreserved with good viability. In a non-human primate model of myocardial ischemia-reperfusion, the cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs resulted in significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over three months, with grafts perfused by host vasculature and electromechanical junctions between graft and host myocytes present within two weeks. The grafts exhibited regular calcium transients synchronized to the host electrocardiogram, indicating electromechanical coupling. However, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates, highlighting potential arrhythmic complications. The study also showed that hESC-CMs could remuscularize substantial amounts of the infarcted monkey heart, suggesting comparable remuscularization in human hearts is possible. The research demonstrated that hESCs can be grown, differentiated into cardiomyocytes, and cryopreserved at a scale sufficient to treat a large animal model of myocardial infarction. The findings highlight the potential of hESC-CMs for heart regeneration but also emphasize the need to address arrhythmic complications for clinical translation. The study used a non-human primate model, which is more clinically relevant than small animal models, and showed that hESC-CMs can be effectively delivered and integrated into the host heart. The research also identified challenges in large-scale production and delivery of hESC-CMs, as well as the need for further studies to validate the maturation of hESC-CMs and their long-term viability. The study provides important insights into the potential of hESC-CMs for heart regeneration and highlights the need for further research to overcome the challenges associated with their clinical application.Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were shown to regenerate non-human primate hearts in a study led by James J.H. Chong and colleagues. The research demonstrated that hESC-CMs could be produced at a clinical scale (>1 billion cells per batch) and cryopreserved with good viability. In a non-human primate model of myocardial ischemia-reperfusion, the cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs resulted in significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over three months, with grafts perfused by host vasculature and electromechanical junctions between graft and host myocytes present within two weeks. The grafts exhibited regular calcium transients synchronized to the host electrocardiogram, indicating electromechanical coupling. However, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates, highlighting potential arrhythmic complications. The study also showed that hESC-CMs could remuscularize substantial amounts of the infarcted monkey heart, suggesting comparable remuscularization in human hearts is possible. The research demonstrated that hESCs can be grown, differentiated into cardiomyocytes, and cryopreserved at a scale sufficient to treat a large animal model of myocardial infarction. The findings highlight the potential of hESC-CMs for heart regeneration but also emphasize the need to address arrhythmic complications for clinical translation. The study used a non-human primate model, which is more clinically relevant than small animal models, and showed that hESC-CMs can be effectively delivered and integrated into the host heart. The research also identified challenges in large-scale production and delivery of hESC-CMs, as well as the need for further studies to validate the maturation of hESC-CMs and their long-term viability. The study provides important insights into the potential of hESC-CMs for heart regeneration and highlights the need for further research to overcome the challenges associated with their clinical application.