Evidence map›Paper›PMID 30597148›Full record

ArticleJournal of molecular and cellular cardiology2019

High-content phenotypic assay for proliferation of human iPSC-derived cardiomyocytes identifies L-type calcium channels as targets.

Laura A Woo, Svyatoslav Tkachenko, Mei Ding, Alleyn T Plowright, Ola Engkvist, Henrik Andersson, Lauren Drowley, Ian Barrett, Mike Firth, Peter Akerblad and 5 more

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation.Journal of cardiovascular development and disease · 2026
    Review
  4. Review
  5. Article
  6. Matured hiPSC-derived cardiomyocytes possess dematuration plasticity.Journal of molecular and cellular cardiology plus · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Advances in Drug Discovery for Cardiomyocyte Proliferation.Current treatment options in cardiovascular medicine · 2025
    Review
  11. Article
  12. Article
  13. Heart rhythmFrontiers in cardiovascular medicine · 2024
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Secretome-Based Screening in Target Discovery.SLAS discovery : advancing life sciences R & D · 2020
    Review
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

15 authors at 3 institutions in 3 countries.

Laura A WooDepartment of Biomedical Engineering and Robert M. Berne Cardiovascular Research Center, University of Virginia, USA.
Svyatoslav TkachenkoDepartment of Biomedical Engineering and Robert M. Berne Cardiovascular Research Center, University of Virginia, USA.
Mei DingDiscovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Alleyn T PlowrightMedicinal Chemistry, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Ola EngkvistDiscovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Henrik AnderssonDiscovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Lauren DrowleyBioscience Heart Failure, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Ian BarrettDiscovery Sciences, IMED Biotech Unit, AstraZeneca Cambridge, UK.
Mike FirthDiscovery Sciences, IMED Biotech Unit, AstraZeneca Cambridge, UK.
Peter AkerbladBioscience Heart Failure, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Matthew J WolfDepartment of Medicine and Robert M. Berne Cardiovascular Research Center, University of Virginia, USA.
Stefan BekiranovDepartment of Biochemistry and Molecular Genetics, University of Virginia, USA.
David L BrautiganCenter for Cell Signaling, Department of Microbiology, Immunology & Cancer Biology, University of Virginia, USA.
Qing-Dong WangBioscience Heart Failure, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca Gothenburg, Sweden.
Jeffrey J SaucermanDepartment of Biomedical Engineering and Robert M. Berne Cardiovascular Research Center, University of Virginia, USA. Electronic address: jsaucerman@virginia.edu.
AstraZeneca (Sweden) · SEUniversity of Virginia · USAstraZeneca (United Kingdom) · GB

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Operetta CLS High-content Imaging SystemS10OD021723 · OD · UNIVERSITY OF VIRGINIA · PI LAZO, JOHN S. · 2017 to 2017
$516k
NHLBI NIH HHS T32 HL007284NIH HHS S10 OD021723
6 · The paper itself

Abstract

Over 5 million people in the United States suffer from heart failure, due to the limited ability to regenerate functional cardiac tissue. One potential therapeutic strategy is to enhance proliferation of resident cardiomyocytes. However, phenotypic screening for therapeutic agents is challenged by the limited ability of conventional markers to discriminate between cardiomyocyte proliferation and endoreplication (e.g. polyploidy and multinucleation). Here, we developed a novel assay that combines automated live-cell microscopy and image processing algorithms to discriminate between proliferation and endoreplication by quantifying changes in the number of nuclei, changes in the number of cells, binucleation, and nuclear DNA content. We applied this assay to further prioritize hits from a primary screen for DNA synthesis, identifying 30 compounds that enhance proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Among the most active compounds from the phenotypic screen are clinically approved L-type calcium channel blockers from multiple chemical classes whose activities were confirmed across different sources of human induced pluripotent stem cell-derived cardiomyocytes. Identification of compounds that stimulate human cardiomyocyte proliferation may provide new therapeutic strategies for heart failure.

Indexed as

Calcium Channels, L-TypeCell ProliferationDNAHumansImage Processing, Computer-AssistedInduced Pluripotent Stem CellsMyocytes, CardiacPhenotypePloidiesCalcium Channels, L-TypeDNACardiomyocyte proliferationHigh-content imagingHuman iPSC-derived cardiomyocytesL-Type calcium channel blockersPhenotypic screen

Identifiers

PMID30597148
PMCPMC6524138
OpenAlexW2907799023

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.