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

Chong, James J. H., Yang, Xiulan, Don, Creighton W., Minami, Elina, Liu, Yen-Wen, Weyers, Jill J., Mahoney, 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. (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature, 510 7504: 273-277. doi:10.1038/nature13233

Author Chong, James J. H.
Yang, Xiulan
Don, Creighton W.
Minami, Elina
Liu, Yen-Wen
Weyers, Jill J.
Mahoney, 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.
Murry, Charles E.
Title Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/nature13233
Open Access Status Not yet assessed
Volume 510
Issue 7504
Start page 273
End page 277
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID P01HL094374
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 379 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 407 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 30 Aug 2016, 20:50:54 EST by Anthony Yeates on behalf of Learning and Research Services (UQ Library)