ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 272 citations in OpenAlex.
- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- Pharmacological study of the safety, efficacy, and potential of M201-A on paroxysmal and persistent atrial fibrillation.The Journal of pharmacology and experimental therapeutics · 2025Trial
- Assessment of Multi-Ion Channel Block in a Phase I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study.Clinical pharmacology and therapeutics · 2019Trial
- Clinical trials in a dish: cardiometabolic drug development with biological and digital twins.The Journal of clinical investigation · 2026Review
- Induced Pluripotent Stem Cell-Based Platforms for Cardiac-Related Pain Research: Molecular Mechanisms, Experimental Models, and Therapeutic Applications.International journal of molecular sciences · 2026Review
- From aging biology to cardiac biotechnology: emerging platforms for modeling cardiac aging.JCI insight · 2026Review
- Mechanical and Electrical Phenotype of hiPSC-Cardiomyocytes on Fibronectin-Based Hydrogels.Advanced healthcare materials · 2026Article
- Co-culturing hiPSC-cardiomyocytes and cardiac fibroblasts enhances engineered heart tissue structure and function.Stem cells translational medicine · 2026Article
- Drug Proarrhythmic Evaluation in a High Throughput Cardiac New Approach Methodology.bioRxiv : the preprint server for biology · 2026Article
- Wave propagation enhances extracellular signal strength in small excitable tissues.Scientific reports · 2026Article
- Personalized in vitro models reveal functional impact of aHeart rhythm O2 · 2026Article
- Paired single-cell imaging of calcium and expression to map niches of identity and function.bioRxiv : the preprint server for biology · 2026Article
- 25 years of applying the 3Rs principles in safety pharmacology: success stories and future perspectives.Frontiers in physiology · 2026Review
- AI-Enabled Reduction of Animal Use in Cardiovascular Translational Medicine: Regulatory and Technological Perspectives.Life (Basel, Switzerland) · 2025Review
- Advanced cardiotoxicity profiling using field potential imaging with UHD-CMOS-MEA in human iPSC-derived cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Reassessing the Conduct of Patch Clamp Cardiac Ion Channel Assays to Improve Nonclinical Data Translation to Clinical ECG Changes and Proarrythmia Risk.Clinical and translational science · 2025Article
- Towards human cardiac new approach methodologies (NAMs) to evaluate the combination of repolarization prolonging and shortening drugs: a pilot study.Frontiers in drug discovery · 2025Article
- Delayed Repolarization Caused by hERG Block With Different Drug Modalities Can Be Detected in Stem Cell-Derived Cardiomyocytes: Incubation Time Matters.Clinical and translational science · 2025Article
- Engineered ACE2 decoy in dry powder form for inhalation: A novel therapy for SARS-CoV-2 variants.Molecular therapy. Methods & clinical development · 2025Article
- DMSO-free cryopreservation of hiPSC-derived cardiomyocytes: low temperature characterization and protocol development.Stem cell research & therapy · 2025Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26 drugs and 3 drug combinations on 2 commercially available iPSC-CM types using high-throughput voltage-sensitive dye and microelectrode-array assays being studied for the CiPA initiative and compared the results with clinical QT prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis comparing iPSC-CMs to clinical trial results demonstrated good correlation between drug-induced rate-corrected action potential duration and field potential duration (APDc and FPDc) prolongation and clinical trial QTc prolongation. Of 20 drugs studied that exhibit clinical QTc prolongation, 17 caused APDc prolongation (16 in Cor.4U and 13 in iCell cardiomyocytes) and 16 caused FPDc prolongation (16 in Cor.4U and 10 in iCell cardiomyocytes). Of 14 drugs that cause TdP, arrhythmias occurred with 10 drugs. Lack of arrhythmic beating in iPSC-CMs for the four remaining drugs could be due to differences in relative levels of expression of individual ion channels. iPSC-CMs responded consistently to human ether-a-go-go potassium channel blocking drugs (APD prolongation and arrhythmias) and calcium channel blocking drugs (APD shortening and prevention of arrhythmias), with a more variable response to late sodium current blocking drugs. Current results confirm the potential of iPSC-CMs for proarrhythmia prediction under CiPA, where iPSC-CM results would serve as a check to ion channel and in silico modeling prediction of proarrhythmic risk. A multi-site validation study is warranted.
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Registered trials
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