Evidence map›Paper›PMID 33648345›Full record

ArticleCirculation2021

Human Engineered Heart Tissue Patches Remuscularize the Injured Heart in a Dose-Dependent Manner.

Eva Querdel, Marina Reinsch, Liesa Castro, Deniz Köse, Andrea Bähr, Svenja Reich, Birgit Geertz, Bärbel Ulmer, Mirja Schulze, Marc D Lemoine and 19 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
20.7field-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

77 citing papers in PubMed, 133 citations in OpenAlex.

  1. Article
  2. Review
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  4. Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026
    Review
  5. Review
  6. Review
  7. Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026
    Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Heart Regeneration for Clinical Application.Internal medicine (Tokyo, Japan) · 2026
    Review
  13. Refining the Guinea Pig (Cavia porcellus) Cryo-Injury Model for Cardiac Regeneration and Functional Characterization.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025
    Article
  14. Article
  15. Article
  16. Review
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 3 institutions in 2 countries.

Eva Querdel *Department of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Marina Reinsch *Department of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Liesa Castro *Department of Cardiovascular Surgery, University Heart Center (L.C., S.P., H.R.), University Medical Center, Hamburg-Eppendorf, Germany.
Deniz KöseDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Andrea BährI. Medizinische Klinik & Poliklinik, University Clinic Rechts der Isar (A.B., N.H., N.K., C.K.), Technical University Munich, Germany.
Svenja ReichDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Birgit GeertzDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Bärbel UlmerDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Mirja SchulzeDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Marc D LemoineGerman Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck (E.Q., M.R., L.C., D.K., B.U., M.S., M.D.L., T.K., M.L., J.S., A.S., T.S., M. Köhne, C.v.B., S.P., I.M., T.C., H.R., A.H., T.E., F.W.).
Tobias KrauseDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Marta LemmeDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Jascha SaniDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Aya ShibamiyaDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Tim StüdemannDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Maria KöhneGerman Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck (E.Q., M.R., L.C., D.K., B.U., M.S., M.D.L., T.K., M.L., J.S., A.S., T.S., M. Köhne, C.v.B., S.P., I.M., T.C., H.R., A.H., T.E., F.W.).
Constantin von BibraDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Nadja HornaschewitzI. Medizinische Klinik & Poliklinik, University Clinic Rechts der Isar (A.B., N.H., N.K., C.K.), Technical University Munich, Germany.
Simon PechaDepartment of Cardiovascular Surgery, University Heart Center (L.C., S.P., H.R.), University Medical Center, Hamburg-Eppendorf, Germany.
Yusuf NejahsieDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Ingra MannhardtDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Torsten ChristDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Hermann ReichenspurnerDepartment of Cardiovascular Surgery, University Heart Center (L.C., S.P., H.R.), University Medical Center, Hamburg-Eppendorf, Germany.
Arne HansenDepartment of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Nikolai KlymiukI. Medizinische Klinik & Poliklinik, University Clinic Rechts der Isar (A.B., N.H., N.K., C.K.), Technical University Munich, Germany.
M KraneDepartment of Cardiovascular Surgery, German Heart Centre Munich (M. Krane), Technical University Munich, Germany.
C KupattI. Medizinische Klinik & Poliklinik, University Clinic Rechts der Isar (A.B., N.H., N.K., C.K.), Technical University Munich, Germany.
Thomas Eschenhagen *Department of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Florian Weinberger *Department of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Universität Hamburg · DETUM Klinikum · DESan Diego Cardiac Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman engineered heart tissue (EHT) transplantation represents a potential regenerative strategy for patients with heart failure and has been successful in preclinical models. Clinical application requires upscaling, adaptation to good manufacturing practices, and determination of the effective dose.

methodsCardiomyocytes were differentiated from 3 different human induced pluripotent stem cell lines including one reprogrammed under good manufacturing practice conditions. Protocols for human induced pluripotent stem cell expansion, cardiomyocyte differentiation, and EHT generation were adapted to substances available in good manufacturing practice quality. EHT geometry was modified to generate patches suitable for transplantation in a small-animal model and perspectively humans. Repair efficacy was evaluated at 3 doses in a cryo-injury guinea pig model. Human-scale patches were epicardially transplanted onto healthy hearts in pigs to assess technical feasibility.

resultsWe created mesh-structured tissue patches for transplantation in guinea pigs (1.5×2.5 cm, 9-15×10

conclusionsEHT patch transplantation resulted in a partial remuscularization of the injured heart and improved left ventricular function in a dose-dependent manner in a guinea pig injury model. Human-scale patches were successfully transplanted in pigs in a proof-of-principle study.

Indexed as

AnimalsDisease Models, AnimalGuinea PigsHumansMyocardiumMyocytes, CardiacTissue Engineeringcell transplantationregenerative medicinestem cells

Identifiers

PMID33648345
PMCPMC8126500
OpenAlexW3135845151

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.