ArticleALTEX2018
A human population-based organotypic in vitro model for cardiotoxicity screening.
Article in ALTEX, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 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
- A Deep Learning-Based Scoring Framework for Large-Scale Multi-Donor Cardiotoxicity Screening.bioRxiv : the preprint server for biology · 2026Article
- Heterogeneity and optimal study design between cell lines in induced pluripotent stem cell-based cardiac disease modeling.Stem cells translational medicine · 2026Review
- A Deep-Learning-Based Scoring Framework for Large-Scale Multi-donor Cardiotoxicity Screening.Computational and structural biotechnology journal · 2026Article
- 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
- Hepatocytes derived from human induced pluripotent stem cells: Towards establishing anCurrent research in toxicology · 2025Article
- Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy.Human genomics · 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
- Technical evaluation and standardization of the human thyroid microtissue assay.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.Regulatory toxicology and pharmacology : RTP · 2024Article
- Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation.Science advances · 2024Article
- Challenging the status quo: a framework for mechanistic and human-relevant cardiovascular safety screening.Frontiers in toxicology · 2024Review
- Article
- Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells.Cell biology and toxicology · 2023Article
- The Advantages, Challenges, and Future of Human-Induced Pluripotent Stem Cell Lines in Type 2 Long QT Syndrome.Journal of cardiovascular translational research · 2023Review
- Beyond pharmaceuticals: Fit-for-purpose new approach methodologies for environmental cardiotoxicity testing.ALTEX · 2023Review
- Article
- In vitro-in silico-based prediction of inter-individual and inter-ethnic variations in the dose-dependent cardiotoxicity of R- and S-methadone in humans.Archives of toxicology · 2022Article
- Integrating nonlinear analysis and machine learning for human induced pluripotent stem cell-based drug cardiotoxicity testing.Journal of tissue engineering and regenerative medicine · 2022Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Assessing inter-individual variability in responses to xenobiotics remains a substantial challenge, both in drug development with respect to pharmaceuticals and in public health with respect to environmental chemicals. Although approaches exist to characterize pharmacokinetic variability, there are no methods to routinely address pharmacodynamic variability. In this study, we aimed to demonstrate the feasibility of characterizing inter-individual variability in a human in vitro model. Specifically, we hypothesized that genetic variability across a population of iPSC-derived cardiomyocytes translates into reproducible variability in both baseline phenotypes and drug responses. We measured baseline and drug-related effects in iPSC-derived cardiomyocytes from 27 healthy donors on kinetic Ca2+ flux and high-content live cell imaging. Cells were treated in concentration-response with cardiotoxic drugs: isoproterenol (β-adrenergic receptor agonist/positive inotrope), propranolol (β-adrenergic receptor antagonist/negative inotrope), and cisapride (hERG channel inhibitor/QT prolongation). Cells from four of the 27 donors were further evaluated in terms of baseline and treatment-related gene expression. Reproducibility of phenotypic responses was evaluated across batches and time. iPSC-derived cardiomyocytes exhibited reproducible donor-specific differences in baseline function and drug-induced effects. We demonstrate the feasibility of using a panel of population-based organotypic cells from healthy donors as an animal replacement experimental model. This model can be used to rapidly screen drugs and chemicals for inter-individual variability in cardiotoxicity. This approach demonstrates the feasibility of quantifying inter-individual variability in xenobiotic responses, and can be expanded to other cell types for which in vitro populations can be derived from iPSCs.
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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.