ArticleToxicology and applied pharmacology2019
Population-based toxicity screening in human induced pluripotent stem cell-derived cardiomyocytes.
Article in Toxicology and applied pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Disturbed mitochondrial maturation in cardiolipin remodeling-deficient cardiomyocytes.iScience · 2026Article
- Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility.bioRxiv : the preprint server for biology · 2025Article
- Drying of Functional Hydrogels: Development of a Workflow for Bioreactor-Integrated Freeze-Drying of Protein-Coated Alginate Microcarriers for iPS Cell-Based Screenings.Gels (Basel, Switzerland) · 2025Article
- Reducing uncertainty in dose-response assessments by incorporating Bayesian benchmark dose modeling and in vitro data on population variability.Risk analysis : an official publication of the Society for Risk Analysis · 2025Article
- Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025Review
- Bridging the gaps in detection of structural cardiotoxicity in stem cell-derived cardiomyocytes: promise of miR-133b, miR-184 and miR-208b-3p.Frontiers in pharmacology · 2025Article
- Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies.Human genomics · 2024Review
- Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy.Human genomics · 2024Article
- Seminar: Functional Exposomics and Mechanisms of Toxicity-Insights from Model Systems and NAMs.Environmental health perspectives · 2024Review
- In vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.Chemical research in toxicology · 2024Article
- Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs-a proof-of-concept study with doxorubicin.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Mapping Interindividual Variability of Toxicodynamics Using High-Throughput Transcriptomics and Primary Human Hepatocytes from Fifty Donors.Environmental health perspectives · 2024Article
- Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.Regulatory toxicology and pharmacology : RTP · 2024Article
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- New approach methodologies to address population variability and susceptibility.Human genomics · 2023Article
- A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides.Nature communications · 2023Article
- Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment.Environmental health : a global access science source · 2023Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The potential for cardiotoxicity is carefully evaluated for pharmaceuticals, as it is a major safety liability. However, environmental chemicals are seldom tested for their cardiotoxic potential. Moreover, there is a large variability in both baseline and drug-induced cardiovascular risk in humans, but data are lacking on the degree to which susceptibility to chemically-induced cardiotoxicity may also vary. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes have become an important in vitro model for drug screening. Thus, we hypothesized that a population-based model of iPSC-derived cardiomyocytes from a diverse set of individuals can be used to assess potential hazard and inter-individual variability in chemical effects on these cells. We conducted concentration-response screening of 134 chemicals (pharmaceuticals, industrial and environmental chemicals and food constituents) in iPSC-derived cardiomyocytes from 43 individuals, comprising both sexes and diverse ancestry. We measured kinetic calcium flux and conducted high-content imaging following chemical exposure, and utilized a panel of functional and cytotoxicity parameters in concentration-response for each chemical and donor. We show reproducible inter-individual variability in both baseline and chemical-induced effects on iPSC-derived cardiomyocytes. Further, chemical-specific variability in potency and degree of population variability were quantified. This study shows the feasibility of using an organotypic population-based human in vitro model to quantitatively assess chemicals for which little cardiotoxicity information is available. Ultimately, these results advance in vitro toxicity testing methodologies by providing an innovative tool for population-based cardiotoxicity screening, contributing to the paradigm shift from traditional animal models of toxicity to in vitro toxicity testing methods.
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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.