Evidence map›Paper›PMID 37028405›Full record

ArticleCell stem cell2023

Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.

Silvia Marchiano, Kenta Nakamura, Hans Reinecke, Lauren Neidig, Michael Lai, Shin Kadota, Filippo Perbellini, Xiulan Yang, Jordan M Klaiman, Leslie P Blakely and 20 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Cell stem cell, 2023. 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 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
11.7field-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

44 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
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  10. Article
  11. Heart Regeneration for Clinical Application.Internal medicine (Tokyo, Japan) · 2026
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. 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
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 4 institutions in 2 countries.

Silvia MarchianoInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Kenta NakamuraInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Hans ReineckeInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Lauren NeidigInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Michael LaiSana Biotechnology, Seattle, WA 98102, USA.
Shin KadotaInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Regenerative Science and Medicine, Shinshu University, Matsumoto 390-8621, Japan.
Filippo PerbelliniSana Biotechnology, Seattle, WA 98102, USA.
Xiulan YangInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Jordan M KlaimanInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Leslie P BlakelyInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Elaheh KarbassiInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Paul A FieldsInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Adaptive Biotechnologies, Seattle, WA 98102, USA.
Aidan M FenixInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Kevin M BeussmanInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Mechanical Engineering, University of Washington, 3720 15(th) Avenue NE, Seattle, WA 98105, USA.
Anu JayabaluInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Faith A KaluckiInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Jennifer C PotterInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Akiko Futakuchi-TsuchidaInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Gerhard J WeberInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Sarah DuprasInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Hiroshi TsuchidaInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Lil PabonInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Lili WangDivision of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Björn C KnollmannDivision of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Steven KattmanInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
R Scott ThiesInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA.
Nathan SniadeckiInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Department of Mechanical Engineering, University of Washington, 3720 15(th) Avenue NE, Seattle, WA 98105, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
W Robb MacLellanInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Alessandro BerteroInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.
Charles E MurryInstitute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Brotman Building Room 453, Seattle, WA 98109, USA; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Sana Biotechnology, Seattle, WA 98102, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. Electronic address: murry@uw.edu.
University of Washington · USSana Biotechnology (United States) · USVanderbilt University · USAdaptive Biotechnologies (United States) · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Karin E Bornfeldt · 1986 to 2026
$41.4M
Toward a Mechanism-Based Approach to Treating Cardiac ArrhythmiaR35HL144980 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KNOLLMANN, BJORN C · 2019 to 2025
$7.1M
Engineered Stem Cells for Cardiac RepairR01HL128368 · NHLBI · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2018 to 2025
$6.1M
Mechanisms of Cell-Based Heart RegenerationR01HL146868 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E, SNIADECKI, NATHAN JOHN · 2019 to 2022
$3.5M
Metabolic and Transcriptional Reprogramming of Cardiac MaturationR01HL148081 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2021 to 2024
$2.5M
NHLBI NIH HHS R01 HL128368NHLBI NIH HHS R01 HL146868NHLBI NIH HHS R01 HL148081NHLBI NIH HHS R35 HL144980NIDDK NIH HHS P30 DK017047
6 · The paper itself

Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer a promising cell-based therapy for myocardial infarction. However, the presence of transitory ventricular arrhythmias, termed engraftment arrhythmias (EAs), hampers clinical applications. We hypothesized that EA results from pacemaker-like activity of hPSC-CMs associated with their developmental immaturity. We characterized ion channel expression patterns during maturation of transplanted hPSC-CMs and used pharmacology and genome editing to identify those responsible for automaticity in vitro. Multiple engineered cell lines were then transplanted in vivo into uninjured porcine hearts. Abolishing depolarization-associated genes HCN4, CACNA1H, and SLC8A1, along with overexpressing hyperpolarization-associated KCNJ2, creates hPSC-CMs that lack automaticity but contract when externally stimulated. When transplanted in vivo, these cells engrafted and coupled electromechanically with host cardiomyocytes without causing sustained EAs. This study supports the hypothesis that the immature electrophysiological prolife of hPSC-CMs mechanistically underlies EA. Thus, targeting automaticity should improve the safety profile of hPSC-CMs for cardiac remuscularization.

Indexed as

Gene EditingMyocytes, CardiacAnimalsArrhythmias, CardiacCell- and Tissue-Based TherapyCell DifferentiationCell LineHumansSwinearrhythmiaautomaticitycardiac remuscularizationcell therapyengraftment arrhythmiaheart regenerationhPSC-CM maturationhuman pluripotent stem cell-derived cardiomyocytesmyocardial infarctionpacemaker

Identifiers

PMID37028405
PMCPMC10283080
OpenAlexW4362664223

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.