Evidence map›Paper›PMID 30413796›Full record

ArticleNature protocols2018

Use of human induced pluripotent stem cell-derived cardiomyocytes to assess drug cardiotoxicity.

Arun Sharma, Wesley L McKeithan, Ricardo Serrano, Tomoya Kitani, Paul W Burridge, Juan C Del Álamo, Mark Mercola, Joseph C Wu

Abstract read
In one paragraph

Article in Nature protocols, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
–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

95 citing papers in PubMed.

  1. Article
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  8. Review
  9. Uncertainty-aware traction force microscopy.PLoS computational biology · 2025
    Article
  10. Review
  11. Article
  12. Modeling immune checkpoint inhibitor associated myocarditisJournal of molecular and cellular cardiology plus · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Field Guide to Traction Force Microscopy.Cellular and molecular bioengineering · 2024
    Review
  20. Article

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

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

8 authors.

Arun SharmaStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-0607-5455
Wesley L McKeithanStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4413-6068
Ricardo SerranoDepartment of Mechanical and Aerospace Engineering, University of California, San Diego, San Diego, CA, USA.
Tomoya KitaniStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Paul W BurridgeDepartment of Pharmacology and Center for Pharmacogenomics, Northwestern University School of Medicine, Chicago, IL, USA.
Juan C Del ÁlamoDepartment of Mechanical and Aerospace Engineering, University of California, San Diego, San Diego, CA, USA.
Mark MercolaStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. joewu@stanford.edu.

Funding

Biorepository of Human iPSCs for Studying Dilated and Hypertrophic CardiomyopathyR24HL117756 · NHLBI · STANFORD UNIVERSITY · PI BUSTAMANTE, CARLOS DANIEL, SNYDER, MICHAEL P. · 2014 to 2018
$8.8M
Elucidating Mechanism of Cardiac Fibrosis with Cell Village of Pooled Human iPSCsR01HL130020 · NHLBI · STANFORD UNIVERSITY · PI Ronglih Liao, MARK MERCOLA · 2016 to 2026
$7.3M
Modeling Susceptibility to Chemotherapy-Induced Cardiotoxicity Using Human iPSCsR01HL123968 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS, WU, JOSEPH C. · 2014 to 2021
$4.8M
MicroRNA Control of Dilated CardiomyopathyR01HL130840 · NHLBI · STANFORD UNIVERSITY · PI MARK MERCOLA, Shankar Subramaniam · 2016 to 2026
$4.6M
A Systems Biology Approach to Study Cardiac Arrhythmias: iPS Cells and In Silico ModelingR01HL128170 · NHLBI · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, CLANCY, COLLEEN E · 2015 to 2018
$3.0M
Role of miR25 in Heart FailureR01HL128072 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J., MERCOLA, MARK · 2015 to 2018
$2.5M
Assessment of Low-Dose Radiation Risk and Mechanisms of Individual RadiosensitivityR01HL132875 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2016 to 2019
$1.9M
Small Molecule NOTCH Inhibitors for the treatment of pulmonary hypertensionR01HL132225 · NHLBI · STANFORD UNIVERSITY · PI MERCOLA, MARK, THISTLETHWAITE, PATRICIA A · 2016 to 2019
$1.7M
A Multiscale Modeling Approach to Hypoplastic Left Heart SyndromeR01HL128630 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEL ALAMO, JUAN CARLOS, NIGAM, VISHAL · 2016 to 2019
$1.5M
NHLBI NIH HHS R01 HL123968NHLBI NIH HHS R01 HL128072NHLBI NIH HHS R01 HL128170NHLBI NIH HHS R01 HL128630NHLBI NIH HHS R01 HL130020NHLBI NIH HHS R01 HL130840NHLBI NIH HHS R01 HL132225NHLBI NIH HHS R01 HL132875NHLBI NIH HHS R24 HL117756
6 · The paper itself

Abstract

Cardiotoxicity has historically been a major cause of drug removal from the pharmaceutical market. Several chemotherapeutic compounds have been noted for their propensities to induce dangerous cardiac-specific side effects such as arrhythmias or cardiomyocyte apoptosis. However, improved preclinical screening methodologies have enabled cardiotoxic compounds to be identified earlier in the drug development pipeline. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to screen for drug-induced alterations in cardiac cellular contractility, electrophysiology, and viability. We previously established a novel 'cardiac safety index' (CSI) as a metric that can evaluate potential cardiotoxic drugs via high-throughput screening of hiPSC-CMs. This metric quantitatively examines drug-induced alterations in CM function, using several in vitro readouts, and normalizes the resulting toxicity values to the in vivo maximum drug blood plasma concentration seen in preclinical or clinical pharmacokinetic models. In this ~1-month-long protocol, we describe how to differentiate hiPSCs into hiPSC-CMs and subsequently implement contractility and cytotoxicity assays that can evaluate drug-induced cardiotoxicity in hiPSC-CMs. We also describe how to carry out the calculations needed to generate the CSI metric from these quantitative toxicity measurements.

Indexed as

CardiotoxicityCell DifferentiationCells, CulturedCell SurvivalDrug Evaluation, PreclinicalHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsMyocardial ContractionMyocytes, CardiacToxicity Tests

Identifiers

PMID30413796
PMCPMC6502639

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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.