Evidence map›Paper›PMID 26503464›Full record

ArticleCirculation research2016

Bioengineering Human Myocardium on Native Extracellular Matrix.

Jacques P Guyette, Jonathan M Charest, Robert W Mills, Bernhard J Jank, Philipp T Moser, Sarah E Gilpin, Joshua R Gershlak, Tatsuya Okamoto, Gabriel Gonzalez, David J Milan and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

155 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Early-Phase Clinical Trials of Bio-Artificial Organ Technology: A Systematic Review of Ethical Issues.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Pooled it
  3. Pooled it
  4. Review
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  6. Article
  7. Article
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  9. Article
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  11. Article
  12. Stimuli-responsive hybrid materials for 4DMaterials today. Bio · 2025
    Review
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  15. Review
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  17. Biocompatibility of decellularized spinach leaves.npj biomedical innovations · 2025
    Article
  18. Review
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jacques P GuyetteFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Jonathan M CharestFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Robert W MillsFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Bernhard J JankFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Philipp T MoserFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Sarah E GilpinFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Joshua R GershlakFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Tatsuya OkamotoFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Gabriel GonzalezFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
David J MilanFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Glenn R GaudetteFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.).
Harald C OttFrom the Center for Regenerative Medicine (J.P.G., J.M.C., B.J.J., P.T.M., S.E.G., T.O., G.G., H.C.O.), Cardiovascular Research Center (R.W.M., D.J.M.), Division of Cardiology (D.J.M.), and Division of Thoracic Surgery, Department of Surgery (H.C.O.), Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA (J.P.G., B.J.J., P.T.M., S.E.G., G.G., H.C.O.); Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA (J.R.G., G.R.G.); and Harvard Stem Cell Institute, Cambridge, MA (H.C.O.). hott@partners.org.

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Transgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FLOREZ, JOSE CARLOS · 2000 to 2019
$31.4M
Skeletal Phenotyping CoreP30AR066261 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DIVIETI PAJEVIC, PAOLA · 2014 to 2018
$3.5M
Organ engineering based on perfusion decellularized matrixDP2OD008749 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI OTT, HARALD C · 2011 to 2011
$2.6M
Biological sutures to enhance progenitor cell delivery and retention in the heartR01HL115282 · NHLBI · WORCESTER POLYTECHNIC INSTITUTE · PI GAUDETTE, GLENN R · 2013 to 2017
$1.9M
Generation of human myocardium from native ECM scaffolds and adult derived cellsR21HL108663 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI OTT, HARALD C · 2011 to 2012
$437k
NHLBI NIH HHS R01 HL115282NHLBI NIH HHS R21 HL108663NHLBI NIH HHS R21 HL108663-2NIAMS NIH HHS P30 AR066261NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIH HHS DP2 OD008749NIH HHS DP2 OD008749-01
6 · The paper itself

Abstract

rationaleMore than 25 million individuals have heart failure worldwide, with ≈4000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only ≈2500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure.

objectiveThe objective of this study is to translate previous work to human scale and clinically relevant cells for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human induced pluripotent stem cell-derived cardiomyocytes. METHODS AND

resultsTo provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiomyocytes derived from nontransgenic human induced pluripotent stem cells and generated tissues of increasing 3-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole-heart scaffolds with human induced pluripotent stem cell-derived cardiomyocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure development, and metabolic function.

conclusionsNative cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human induced pluripotent stem cell-derived cardiomyocytes and enable the bioengineering of functional human myocardial-like tissue of multiple complexities.

Indexed as

AdultAgedBioengineeringCell DifferentiationExtracellular MatrixFemaleHumansMaleMiddle AgedMyocardiumPluripotent Stem Cellscardiomyocytesextracellular matrixinduced pluripotent stem cellsregeneration

Identifiers

PMID26503464
PMCPMC4740234

What OpenQuestion holds

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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.