Evidence map›Paper›PMID 24776797›Full record

ArticleNature2014

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 and 15 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 785 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
785citing papers in PubMed, 4 pooled it
71.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

785 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,398 citations in OpenAlex.

  1. Pooled it
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  18. Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026
    Review
  19. Circumferential strain recovery after human cardiomyocyte transplantation in minipigs using a novel frequency-based method for myocardial tagging quantification.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2026
    Article
  20. Review

725 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 2 institutions in 1 country.

James J H Chong1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Cardiology Westmead Hospital, Westmead, New South Wales 2145, Australia [4] School of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia [5] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [6] University of Sydney School of Medicine, Sydney, New South Wales 2006, Australia and Westmead Millennium Institute and Westmead Hospital, Westmead, New South Wales 2145, Australia.
Xiulan Yang1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Creighton W DonDepartment of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, USA.
Elina Minami1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [4] Department of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, USA.
Yen-Wen Liu1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Jill J Weyers1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
William M Mahoney1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Benjamin Van Biber1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Savannah M CookDepartment of Comparative Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA.
Nathan J Palpant1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Jay A Gantz1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [4] Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
James A Fugate1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Veronica Muskheli1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
G Michael GoughWashington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
Keith W VogelWashington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
Cliff A AstleyWashington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
Charlotte E HotchkissWashington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
Audrey BaldessariWashington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
Lil Pabon1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Hans Reinecke1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Edward A GillDepartment of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, USA.
Veronica NelsonFred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Hans-Peter Kiem1] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [2] Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Michael A Laflamme1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Charles E Murry1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [4] Department of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, USA [5] Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
University of Washington · USFred Hutch Cancer Center · US

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Julie Mathieu · 1986 to 2026
$41.4M
University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2007 to 2017
$20.6M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2010 to 2014
$14.5M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
Cell-Based Cardiac RepairR01HL084642 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2007 to 2014
$4.9M
Integration and Arrhythmia Suppression with hESC-Derived Cardiomyocyte GraftsR01HL117991 · NHLBI · UNIVERSITY OF WASHINGTON · PI LAFLAMME, MICHAEL ALAN · 2013 to 2015
$1.2M
RESEARCH TRAINING IN PHYSIOLOGICAL ADAPTATION TO STRESST32GM008619 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI JEFFERSON, LEONARD S · 1996 to 2005
$976k
NHLBI NIH HHS P01 HL094374NHLBI NIH HHS P01HL094374NHLBI NIH HHS R01 HL084642NHLBI NIH HHS R01HL084642NHLBI NIH HHS R01 HL117991NHLBI NIH HHS U01 HL100405NHLBI NIH HHS U01HL100405NIDDK NIH HHS P30 DK017047NIGMS NIH HHS P01 GM081619NIGMS NIH HHS P01GM081619NIGMS NIH HHS T32 GM007266NIH HHS P51 OD010425
6 · The paper itself

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.

Indexed as

HeartRegenerationAnimalsArrhythmias, CardiacCalciumCell SurvivalCoronary VesselsCryopreservationDisease Models, AnimalElectrocardiographyEmbryonic Stem CellsHumansMacaca nemestrinaMaleMiceMyocardial InfarctionCalcium

Identifiers

PMID24776797
PMCPMC4154594
OpenAlexW2086294280

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.