ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Detection of Drug-Induced Torsades de Pointes Arrhythmia Mechanisms Using hiPSC-CM Syncytial Monolayers in a High-Throughput Screening Voltage Sensitive Dye Assay.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 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
- Discovery of Ro 41-0960, a Non-Steroidal Inhibitor of the NaChemMedChem · 2026Article
- A machine learning platform for genotype-specific cardiotoxicity risk prediction using patient-derived iPSC-CMs.Journal of advanced research · 2026Article
- Advanced physiological maturation of human iPSC-derived cardiomyocytes using an algorithm-directed optimization of defined media components.Nature communications · 2026Article
- Response of human iPSC-cardiomyocytes to adrenergic drugs assessed by high-throughput pericellular oxygen measurements and computational modeling.Journal of molecular and cellular cardiology plus · 2026Article
- From Vision to Reality: Five Years of the Botanical Safety Consortium.Pharmaceutical biology · 2025Review
- Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe.Scientific reports · 2025Article
- Effect of electrochemical topology on detection sensitivity in MEA assay for drug-induced cardiotoxicity screening.Biosensors & bioelectronics · 2025Article
- Developing an approach for evaluating the cardiotoxic potential of botanicals.Frontiers in toxicology · 2025Review
- The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies.International journal of molecular sciences · 2024Review
- hiPSC-CM electrophysiology: impact of temporal changes and study parameters on experimental reproducibility.American journal of physiology. Heart and circulatory physiology · 2024Article
- Three-dimensional cardiac models: a pre-clinical testing platform.Biochemical Society transactions · 2024Review
- Bipolar Patient-Specific In Vitro Diagnostic Test Reveals Underlying Cardiac Arrhythmia Phenotype Caused by Calcium Channel Genetic Risk Factor.Biological psychiatry global open science · 2024Article
- High-throughput longitudinal electrophysiology screening of mature chamber-specific hiPSC-CMs using optical mapping.iScience · 2023Article
- Article
- Establishment and validation of a torsade de pointes prediction model based on human iPSC‑derived cardiomyocytes.Experimental and therapeutic medicine · 2023Article
- Beyond pharmaceuticals: Fit-for-purpose new approach methodologies for environmental cardiotoxicity testing.ALTEX · 2023Review
- Enhancing iPSC-CM Maturation Using a Matrigel-Coated Micropatterned PDMS Substrate.Current protocols · 2022Article
- Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.Journal of the American Heart Association · 2022Review
- Human iPSC-Cardiomyocytes as an Experimental Model to Study Epigenetic Modifiers of Electrophysiology.Cells · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We validated 3 distinct hiPSC-CM cell lines-each of different purity and a voltage sensitive dye (VSD)-based high-throughput proarrhythmia screening assay as a noncore site in the recently completed CiPA Myocyte Phase II Validation Study. Blinded validation was performed using 12 drugs linked to low, intermediate, or high risk for causing Torsades de Pointes (TdP). Commercially sourced hiPSC-CMs were obtained either from Cellular Dynamics International (CDI, Madison, Wisconsin, iCell Cardiomyoyctes2) or Takara Bio (CLS, Cellartis Cardiomyocytes). A third hiPSC-CM cell line (MCH, Michigan) was generated in house. Each cell type had distinct baseline electrophysiological function (spontaneous beat rate, action potential duration, and conduction velocity) and drug responsiveness. Use of VSD and optical mapping enabled the detection of conduction slowing of sodium channel blockers (quinidine, disopyramide, and mexiletine) and drug-induced TdP-like activation patterns (rotors) for some high- and intermediate-risk compounds. Low-risk compounds did not induce rotors in any cell type tested. These results further validate the utility of hiPSC-CMs for predictive proarrhythmia screening and the utility of VSD technology to detect drug-induced APD prolongation, arrhythmias (rotors), and conduction slowing. Importantly, results indicate that different ratios of cardiomyocytes and noncardiomyocytes have important impact on drug response that may be considered during risk assessment of new drugs. Finally, we present the first blinded CiPA hiPSC-CM validation results to simultaneously detect drug-induced conduction slowing, action potential duration prolongation, action potential triangulation, and drug-induced rotors in a proarrhythmia assay.
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Registered trials
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