Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts

James J.H. Chong, Xiulan Yang, Creighton W. Don, Elina Minami, Yen Wen Liu, Jill J. Weyers, William M. Mahoney, Benjamin Van Biber, Savannah M. Cook, Nathan J. Palpant, Jay A. Gantz, James A. Fugate, Veronica Muskheli, G. Michael Gough, Keith W. Vogel, Cliff A. Astley, Charlotte E. Hotchkiss, Audrey Baldessari, Lil Pabon, Hans ReineckeEdward A. Gill, Veronica Nelson, Hans Peter Kiem, Michael A. Laflamme, Charles E. Murry

Research output: Contribution to journalArticlepeer-review

702 Citations (Scopus)

Abstract

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. 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 intra-myocardial 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, non-fatal 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.

Original languageEnglish
Pages (from-to)273-277
Number of pages5
JournalNature
Volume510
Issue number7504
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • General

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