1. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts
- Author
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Chong, James J.H., Yang, Xiulan, Don, Creighton W., Minami, Elina, Liu, Yen-Wen, Weyers, Jill J., Mahoney, Jr., William M., Van Biber, Benjamin, Cook, Savannah M., Palpant, Nathan J., Gantz, Jay A., Fugate, James A., Muskheli, Veronica, Gough, G. Michael, Vogel, Keith W., Astley, Cliff A., Hotchkiss, Charlotte E., Baldessari, Audrey, Pabon, Lil, Reinecke, Hans, Gill, Edward A., Nelson, Veronica, Kiem, Hans-Peter, Laflamme, Michael A., and Murry, Charles E.
- Subjects
Embryonic stem cells -- Research ,Heart cells -- Research ,Regeneration (Biology) -- Research ,Stem cell research ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure (1) by providing human cardiomyocytes to support heart regeneration (2). Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment (3-7). However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intramyocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models (7),nonfatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome., Human pluripotent stem cells have indisputable cardiomyocyte-generating abilities and have been extensively investigated for repair of the injured heart (3,4,6,10). These stem cells are derived either from developing blastocytsts (human [...]
- Published
- 2014