ArticlePloS one2016
Electrophysiological Characteristics of Human iPSC-Derived Cardiomyocytes for the Assessment of Drug-Induced Proarrhythmic Potential.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 85 citations in OpenAlex.
- Do Stimulants Promote Arrhythmic Risk: Insights From a Human-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model.Journal of arrhythmia · 2026Article
- Metabolic fatty acid substrates enhance the structural and mechanical performance of human-induced pluripotent stem cell-derived cardiomyocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Transparent Graphene Interfaces for Capacitive Recordings from hiPSC-Derived Cardiomyocyte Monolayers: A Proof-of-Concept Study.Sensors (Basel, Switzerland) · 2026Article
- Influence of Cooling Agents on the Arrhythmogenic and Autonomic Effects of Electronic Cigarettes in an in vivo Model.Circulation. Arrhythmia and electrophysiology · 2026Article
- Proarrhythmic Risk Assessment of Sildenafil under High-Dose Misuse Conditions Using the Comprehensive In Vitro Proarrhythmia Assay (CiPA).Biomolecules & therapeutics · 2026Article
- 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
- Computationally informed point of departure evaluation for proarrhythmic cardiotoxicity assessment using 3D engineered cardiac microtissues from human iPSC-derived cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Integral approach to organelle profiling in human iPSC-derived cardiomyocytes enhancesFrontiers in toxicology · 2025Article
- hiPSC-CM electrophysiology: impact of temporal changes and study parameters on experimental reproducibility.American journal of physiology. Heart and circulatory physiology · 2024Article
- Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder.JCI insight · 2024Article
- CardioMEA: comprehensive data analysis platform for studying cardiac diseases and drug responses.Frontiers in physiology · 2024Article
- Article
- Predicting human cardiac QT alterations and pro-arrhythmic effects of compounds with a 3D beating heart-on-chip platform.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- iPSC-Derived Cardiomyocytes in Inherited Cardiac Arrhythmias: Pathomechanistic Discovery and Drug Development.Biomedicines · 2023Review
- Repeated and On-Demand Intracellular Recordings of Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells.ACS sensors · 2022Article
- Validating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System.ACS pharmacology & translational science · 2022Article
- The Challenges of Predicting Drug-Induced QTc Prolongation in Humans.Toxicological sciences : an official journal of the Society of Toxicology · 2022Review
- Deciphering Common Long QT Syndrome Using CRISPR/Cas9 in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in cardiovascular medicine · 2022Review
- Electrophysiological Changes of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes during Acute Hypoxia and Reoxygenation.Stem cells international · 2022Article
- Assessment of human bioengineered cardiac tissue function in hypoxic and re-oxygenized environments to understand functional recovery in heart failure.Regenerative therapy · 2021Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aims of this study were to (1) characterize basic electrophysiological elements of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond to clinical properties such as QT-RR relationship, (2) determine the applicability of QT correction and analysis methods, and (3) determine if and how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects such as Torsades de pointes (TdP). Field potential recordings were obtained from commercially available hiPSC-CMs using multi-electrode array (MEA) platform with and without ion channel antagonists in the recording solution. Under control conditions, MEA-measured interspike interval and field potential duration (FPD) ranged widely from 1049 to 1635 ms and from 334 to 527 ms, respectively and provided positive linear regression coefficients similar to native QT-RR plots obtained from human electrocardiogram (ECG) analyses in the ongoing cardiovascular-based Framingham Heart Study. Similar to minimizing the effect of heart rate on the QT interval, Fridericia's and Bazett's corrections reduced the influence of beat rate on hiPSC-CM FPD. In the presence of E-4031 and cisapride, inhibitors of the rapid delayed rectifier potassium current, hiPSC-CMs showed reverse use-dependent FPD prolongation. Categorical analysis, which is usually applied to clinical QT studies, was applicable to hiPSC-CMs for evaluating torsadogenic risks with FPD and/or corrected FPD. Together, this results of this study links hiPSC-CM electrophysiological endpoints to native ECG endpoints, demonstrates the appropriateness of clinical analytical practices as applied to hiPSC-CMs, and suggests that hiPSC-CMs are a reliable models for assessing the arrhythmogenic potential of drug candidates in human.
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Registered trials
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.