ArticleDrug metabolism and disposition: the biological fate of chemicals2017
Transcriptional, Functional, and Mechanistic Comparisons of Stem Cell-Derived Hepatocytes, HepaRG Cells, and Three-Dimensional Human Hepatocyte Spheroids as Predictive In Vitro Systems for Drug-Induced Liver Injury.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed.
- Assessing drug-induced liver injury liabilities in human and animal hepatocytes under static and perfused spheroid culture conditions.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
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- A Machine Vision-Guided Microphysiological Platform With Automated Microfluidics Enables Longitudinal Biomarker Monitoring and Emulation of Translationally Relevant Exposure Scenarios.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Single-cell transcriptomics of acetaminophen-induced responses in human 2D and 3D liver microtissues.Archives of toxicology · 2026Article
- New approach methodologies to model liver fibrosis in metabolic dysfunction-associated steatohepatitis.BMB reports · 2026Review
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- Exploring the potential of liver microphysiological systems of varied configurations to model cholestatic chemical effects.Archives of toxicology · 2026Article
- Quantitative Systems Toxicology Predicts Ivacaftor-Induced Oxidative Stress Contributes to CFTR Modulator Hepatotoxicity.Clinical pharmacology and therapeutics · 2026Article
- Evaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.Cellular and molecular life sciences : CMLS · 2025Article
- Primary Human Tissue Models for Metabolic Dysfunction-Associated Liver Disease - toward Streamlining Drug Discovery with Patient-Derived Assays.Advanced biology · 2025Review
- Autologous Organoid-T Cell Co-Culture Platform for Modeling of Immune-Mediated Drug-Induced Liver Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evaluation of Elexacaftor/Tezacaftor/Ivacaftor-Mediated Drug-Induced Liver Injury Using a Liver-On-Chip Model.Clinical and translational science · 2025Article
- 3D Culture in Functionalized FN-Silk Networks Facilitate Proliferation, Differentiation and Phenotypic Stability of Mature Human Primary Cells and Stem Cells.Biotechnology and bioengineering · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Hepatotoxicity evaluation method through multiple-factor analysis using human pluripotent stem cell derived hepatic organoids.Scientific reports · 2025Article
- Article
- Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.Autophagy · 2024Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
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Abstract
Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems-hepatocytes derived from induced pluripotent stem cells, HepaRG cells, and three-dimensional primary human hepatocyte (PHH) spheroids-at transcriptional and functional levels in a multicenter study to evaluate their potential as predictive models for drug-induced hepatotoxicity. Transcriptomic analyses revealed widespread gene expression differences between the three cell models, with 8148 of 17,462 analyzed genes (47%) being differentially expressed. Expression levels of genes involved in the metabolism of endogenous as well as xenobiotic compounds were significantly elevated in PHH spheroids, whereas genes involved in cell division and endocytosis were significantly upregulated in HepaRG cells and hepatocytes derived from induced pluripotent stem cells, respectively. Consequently, PHH spheroids were more sensitive to a panel of drugs with distinctly different toxicity mechanisms, an effect that was amplified by long-term exposure using repeated treatments. Importantly, toxicogenomic analyses revealed that transcriptomic changes in PHH spheroids were in compliance with cholestatic, carcinogenic, or steatogenic in vivo toxicity mechanisms at clinically relevant drug concentrations. Combined, the data reveal important phenotypic differences between the three cell systems and suggest that PHH spheroids can be used for functional investigations of drug-induced liver injury in vivo in humans.
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