Evidence map›Paper›PMID 35089805›Full record

ArticleCirculation2022

In Vitro Matured Human Pluripotent Stem Cell-Derived Cardiomyocytes Form Grafts With Enhanced Structure and Function in Injured Hearts.

Wahiba Dhahri, Tamilla Sadikov Valdman, Dan Wilkinson, Elizabeth Pereira, Eylül Ceylan, Naaz Andharia, Beiping Qiang, Hassan Masoudpour, Fanny Wulkan, Elya Quesnel and 10 more

Abstract read
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In one paragraph

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 2 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

71 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
    Pooled it
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  14. 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
  15. Article
  16. 3D Bioprinting Functional Engineered Heart Tissues.International journal of molecular sciences · 2025
    Review
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  20. 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
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Wahiba DhahriMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Tamilla Sadikov ValdmanMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Dan WilkinsonBlueRock Therapeutics, New York (D.W., E.P.).
Elizabeth PereiraBlueRock Therapeutics, New York (D.W., E.P.).
Eylül CeylanMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Naaz AndhariaMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Beiping QiangMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.ORCID 0000-0003-2482-3354
Hassan MasoudpourMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Fanny WulkanMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Elya QuesnelMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Wenlei JiangMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Shunsuke FunakoshiMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Amine MazineMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
M Juliana Gomez-GarciaMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Neda LatifiInstitute of Biomedical Engineering (M.J.G.-G., N.L., C.A.S.), University of Toronto, ON, Canada.ORCID 0000-0002-8099-8354
Yidi JiangBiostatistics Research Unit (Y.J., E.H.), University Health Network, Toronto, ON, Canada.
Ella HusztiBiostatistics Research Unit (Y.J., E.H.), University Health Network, Toronto, ON, Canada.
Craig A SimmonsInstitute of Biomedical Engineering (M.J.G.-G., N.L., C.A.S.), University of Toronto, ON, Canada.ORCID 0000-0001-7729-1772
Gordon KellerMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.
Michael A LaflammeMcEwen Stem Cell Institute (W.D., T.S.V., E.C., N.A., B.Q., H.M., F.W., E.Q., W.J., S.F., A.M., M.J.G.-G., G.K., M.A.L.), University Health Network, Toronto, ON, Canada.ORCID 0000-0001-5908-880X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) have tremendous promise for application in cardiac regeneration, but their translational potential is limited by an immature phenotype. We hypothesized that large-scale manufacturing of mature hPSC-CMs could be achieved through culture on polydimethylsiloxane (PDMS)-lined roller bottles and that the transplantation of these cells would mediate better structural and functional outcomes than with conventional immature hPSC-CM populations.

methodsWe comprehensively phenotyped hPSC-CMs after in vitro maturation for 20 and 40 days on either PDMS or standard tissue culture plastic substrates. All hPSC-CMs were generated from a transgenic hPSC line that stably expressed a voltage-sensitive fluorescent reporter to facilitate in vitro and in vivo electrophysiological studies, and cardiomyocyte populations were also analyzed in vitro by immunocytochemistry, ultrastructure and fluorescent calcium imaging, and bulk and single-cell transcriptomics. We next compared outcomes after the transplantation of these populations into a guinea pig model of myocardial infarction using end points including histology, optical mapping of graft- and host-derived action potentials, echocardiography, and telemetric electrocardiographic monitoring.

resultsWe demonstrated the economic generation of >1×10

conclusionsWe describe practical methods for the scaled generation of mature hPSC-CMs and provide the first evidence that the transplantation of more mature cardiomyocytes yields better outcomes in vivo.

Indexed as

Myocytes, CardiacPluripotent Stem CellsAnimalsCell DifferentiationCell LineGuinea PigsHumansPlasticsPlasticscell transplantationmyocardial infarctionmyocytes, cardiacpluripotent stem cellsregeneration

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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.