期刊
NATURE
卷 510, 期 7504, 页码 273-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nature13233
关键词
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资金
- National Institutes of Health [P01HL094374, R01HL084642, U01HL100405, P01GM081619]
- Institute of Translational Health Sciences/Primate Center Ignition Award
- National Health and Medical Research Council of Australia
- Australian-American Fulbright Commission
- American Heart Association [12POST11940060, 12POST9330030]
- Jose Carreras/E.D. Thomas Chair for Cancer Research
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 infarctedheart. 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.
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