ArticleToxicological sciences : an official journal of the Society of Toxicology2018
Prediction of Drug-Induced Hepatotoxicity Using Long-Term Stable Primary Hepatic 3D Spheroid Cultures in Chemically Defined Conditions.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 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
- Advances and applications of organ-on-a-chip technology.Cell reports methods · 2026Review
- A human liver organoid platform for hepatotoxicity assessment: evaluation using reference compounds.Frontiers in toxicology · 2026Article
- Apoptotic signatures allow early and rapid screening of drug-induced liver injury to accelerate drug discovery.Communications medicine · 2025Article
- Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).International journal of molecular medicine · 2025Review
- In Vitro Assessment of Drug-Induced Liver Injury Using Three-Dimensional Cultured HepaSH Cells Derived From Chimeric Mouse Model With Humanized Liver.Journal of applied toxicology : JAT · 2025Article
- Evaluating cannabidiol-induced liver injury with and without valproate using a three-dimensional human hepatocyte spheroid model.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
- Comparative Analysis of Species-Specific Hepatocyte Function and Drug Effects in a Liver Microphysiological System PhysioMimix LC12 and 96-Well Plates.ACS pharmacology & translational science · 2025Article
- A large-scale human toxicogenomics resource for drug-induced liver injury prediction.Nature communications · 2025Article
- Animal product-free formation and cultivation of three-dimensional primary hepatocyte spheroids.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Improving drug-induced liver injury prediction using graph neural networks with augmented graph features from molecular optimisation.Journal of cheminformatics · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- In vitro-in silico analysis reveals that loss of tankyrase1/2 improves bile acid handling in genetically engineered HepG2 cultures.Archives of toxicology · 2025Article
- Design of optimal concentrations for in vitro cytotoxicity experiments.Archives of toxicology · 2025Article
- Physiological liver microtissue 384-well microplate system for preclinical hepatotoxicity assessment of therapeutic small molecule drugs.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- Isolation and Cryopreservation of Primary Macaque Hepatocytes.Current protocols · 2024Article
- Liver organoids: updates on generation strategies and biomedical applications.Stem cell research & therapy · 2024Review
21 more citing papers are in PubMed but not listed here.
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Abstract
High failure rates of drug candidates in the clinics, restricted-use warnings as well as withdrawals of drugs in postmarketing stages are of substantial concern for the pharmaceutical industry and drug-induced liver injury (DILI) constitutes one of the most frequent reasons for such safety failures. Importantly, as DILI cannot be accurately predicted using animal models, animal safety tests are commonly complemented with assessments in human in vitro systems. 3D spheroid cultures of primary human hepatocytes in chemically defined conditions, hereafter termed CD-spheroids, have recently emerged as a microphysiological model system in which hepatocytes retain their molecular phenotypes and hepatic functions for multiple weeks in culture. However, their predictive power for the detection of hepatotoxic liabilities has not been systematically assessed. Therefore, we here evaluated the hepatotoxicity of 123 drugs with or without direct implication in clinical DILI events. Importantly, using ATP quantifications as the single endpoint, the model accurately distinguished between hepatotoxic and nontoxic structural analogues and exceeded both sensitivity and specificity of all previously published in vitro assays at substantially lower exposure levels, successfully detecting 69% of all hepatotoxic compounds without producing any false positive results (100% specificity). Furthermore, the platform supports the culture of spheroids of primary hepatocytes from preclinical animal models, thereby allowing the identification of animal-specific toxicity events. We anticipate that CD-spheroids represent a powerful and versatile tool in drug discovery and preclinical drug development that can reliably flag hepatotoxic drug candidates and provide guidance for the selection of the most suitable animal models.
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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.