Document Detail


Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.
MedLine Citation:
PMID:  24776797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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 Reinecke; Edward A Gill; Veronica Nelson; Hans-Peter Kiem; Michael A Laflamme; Charles E Murry
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2014-04-30
Journal Detail:
Title:  Nature     Volume:  510     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-06-12     Completed Date:  2014-07-15     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / physiopathology
Calcium / metabolism
Cell Survival
Coronary Vessels / physiology
Cryopreservation
Disease Models, Animal
Electrocardiography
Embryonic Stem Cells / cytology*
Heart*
Humans
Macaca nemestrina
Male
Mice
Myocardial Infarction / pathology*,  therapy*
Myocytes, Cardiac / cytology*
Regeneration*
Regenerative Medicine / methods
Grant Support
ID/Acronym/Agency:
P01 GM081619/GM/NIGMS NIH HHS; P01 HL094374/HL/NHLBI NIH HHS; P01GM081619/GM/NIGMS NIH HHS; P01HL094374/HL/NHLBI NIH HHS; R01 HL084642/HL/NHLBI NIH HHS; R01HL084642/HL/NHLBI NIH HHS; T32 GM007266/GM/NIGMS NIH HHS; U01 HL100405/HL/NHLBI NIH HHS; U01HL100405/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
SY7Q814VUP/Calcium
Comments/Corrections
Comment In:
Circ Res. 2014 Jul 18;115(3):335-8   [PMID:  24935962 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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