Evidence map›Paper›PMID 26291556›Full record

ArticleCirculation research2015

Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model.

Johannes Riegler, Malte Tiburcy, Antje Ebert, Evangeline Tzatzalos, Uwe Raaz, Oscar J Abilez, Qi Shen, Nigel G Kooreman, Evgenios Neofytou, Vincent C Chen and 8 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 1 pooled it
25.4field-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

144 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.

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  15. Pluripotent stem cell-based approaches for heart repair and the potential of genetic modifications.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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84 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 1 institution in 1 country.

Johannes RieglerFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Malte TiburcyFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Antje EbertFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Evangeline TzatzalosFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Uwe RaazFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Oscar J AbilezFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Qi ShenFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Nigel G KooremanFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Evgenios NeofytouFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Vincent C ChenFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Mouer WangFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Tim MeyerFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Philip S TsaoFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Andrew J ConnollyFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Larry A CoutureFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Joseph D GoldFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA.
Wolfram H ZimmermannFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA. joewu@stanford.edu w.zimmermann@med.uni-goettingen.de.
Joseph C WuFrom the Division of Cardiology, Department of Medicine, Stanford Cardiovascular Institute (J.R., A.E., E.T., U.R., O.J.A., O.S., N.G.K., E.N., M.W., P.S.T., J.D.G., J.C.W.) and Department of Pathology (A.J.C.), Stanford University School of Medicine, CA; Department for Research and Development, Veterans Administration Palo Alto Health Care System, CA (P.S.T.); Institute of Pharmacology, Heart Research Center, University Medical Center, Georg-August-University and German Center for Cardiovascular Research, Göttingen, Germany (M.T., T.M., W.H.Z.); and Center for Biomedicine and Genetics (V.C.C., L.A.C.) and Center for Applied Technology Development, Beckman Research Institute (A.J.C.), City of Hope, Duarte, CA. joewu@stanford.edu w.zimmermann@med.uni-goettingen.de.
VA Palo Alto Health Care System · US

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
T32 Training Program in Mechanisms and Innovation in Vascular DiseaseT32HL098049 · NHLBI · STANFORD UNIVERSITY · PI Nicholas James Leeper, Philip S Tsao · 2010 to 2026
$6.3M
Re-Education of the Immune System for hES Cell ToleranceR01AI085575 · NIAID · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2009 to 2013
$2.0M
NHLBI NIH HHS T32 HL098049NHLBI NIH HHS U01 HL099776NHLBI NIH HHS U01 HL099997NIAID NIH HHS R01 AI085575
6 · The paper itself

Abstract

rationaleTissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocyte transplantation, thereby potentially preventing dilative remodeling and progression to heart failure.

objectiveAssessment of transport stability, long-term survival, structural organization, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction model. METHODS AND

resultsWe constructed EHMs from human embryonic stem cell-derived cardiomyocytes and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P=0.83, P=0.87). One month after ischemia/reperfusion injury, EHMs were implanted onto immunocompromised rat hearts to simulate chronic ischemia. Bioluminescence imaging showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67), preserving ≤25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs, -6.7±1.4% versus control, -10.9±1.5%; n>12; P=0.05), we observed no difference between EHMs containing viable and nonviable human cardiomyocytes in this chronic xenotransplantation model (n>12; P=0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring.

conclusionsEHM transplantation led to high engraftment rates, long-term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic myocardial infarction model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation.

Indexed as

Graft SurvivalAnimalsBiomarkersCell DifferentiationCell LineCell SurvivalConnexin 43Disease Models, AnimalEmbryonic Stem CellsHeart TransplantationHeterograftsHumansImmunosuppressive AgentsMaleMyocardial ContractionMyocardial InfarctionBiomarkersConnexin 43GJA1 protein, humanImmunosuppressive Agentscardiac function testscardiac MRIcell survivalmyocardial infarctionmyocardial ischemiatissue engineeringtransplantation

Identifiers

PMID26291556
PMCPMC4679370
OpenAlexW2107124153

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.