ArticleBritish journal of pharmacology2015
Human induced pluripotent stem cell-derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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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.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Gradient-based parameter optimization method to determine membrane ionic current composition in human induced pluripotent stem cell-derived cardiomyocytes.Scientific reports · 2022Trial
- Determining properties of human-induced pluripotent stem cell-derived cardiomyocytes using spatially resolved electromechanical metrics.The Journal of physiology · 2026Article
- In silico modelling of multi-electrode arrays for enhancing cardiac drug testing on hiPSC-CM heterogeneous tissues.The Journal of physiology · 2026Article
- A novel computational model of human iPSC-derived ventricular myocytes with improved L-type calcium current for application to Timothy syndrome.Scientific reports · 2026Article
- Pillar arrays as tunable interfacial barriers for microphysiological systems.Communications engineering · 2025Article
- Arrhythmogenic Risk in iPSC-Derived Cardiomyocytes: Current Limitations and Therapeutic Perspectives.Medicina (Kaunas, Lithuania) · 2025Review
- 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
- A stacking ensemble machine learning model for evaluating cardiac toxicity of drugs based on in silico biomarkers.CPT: pharmacometrics & systems pharmacology · 2024Article
- The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity.International journal of molecular sciences · 2024Review
- Cell-specific models of hiPSC-CMs developed by the gradient-based parameter optimization method fitting two different action potential waveforms.Scientific reports · 2024Article
- In silico study of the mechanisms of hypoxia and contractile dysfunction during ischemia and reperfusion of hiPSC cardiomyocytes.Disease models & mechanisms · 2024Article
- Quercetin is a foe in the heart by targeting the hERG potassium channel.Iranian journal of basic medical sciences · 2024Article
- Non-invasive assessment of proarrhythmic risks associated with isoprenaline and the dietary supplement ingredient synephrine using human induced pluripotent stem cell-derived cardiomyocytes.Frontiers in cardiovascular medicine · 2024Article
- The simplified Kirchhoff network model (SKNM): a cell-based reaction-diffusion model of excitable tissue.Scientific reports · 2023Article
- Building blocks of microphysiological system to model physiology and pathophysiology of human heart.Frontiers in physiology · 2023Review
- Injection of IFrontiers in physiology · 2023Article
- Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips.Nature biomedical engineering · 2022Article
- Yohimbine Directly Induces Cardiotoxicity on Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Cardiovascular toxicology · 2022Article
- Quantitative cross-species translators of cardiac myocyte electrophysiology: Model training, experimental validation, and applications.Science advances · 2021Article
- Human Atrial Cardiac Microtissues for Chamber-Specific Arrhythmic Risk Assessment.Cellular and molecular bioengineering · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
background and purposeTwo new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and in silico human adult ventricular cardiomyocyte (hAdultV-CM) models. Their combination was recently proposed as a potential replacement for the present hERG-based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC-CM and hAdultV-CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. EXPERIMENTAL APPROACH: In silico AP models of ventricular-like and atrial-like hiPSC-CMs and hAdultV-CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. KEY
resultsQualitatively, hiPSC-CM and hAdultV-CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC-CMs were more sensitive to block of (i) L-type Ca(2+) currents due to the overexpression of the Na(+) /Ca(2+) exchanger (leading to shorter APs) and (ii) the inward rectifier K(+) current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). CONCLUSIONS AND IMPLICATIONS: In silico hiPSC-CMs and hAdultV-CMs exhibit a similar response to selective current blocks. However, overall hiPSC-CMs show greater sensitivity to block, which may facilitate in vitro identification of drug-induced effects. Extrapolation of drug effects from hiPSC-CM to hAdultV-CM and pro-arrhythmic risk assessment can be facilitated by in silico predictions using biophysically-based computational models.
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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.