ArticleToxicological sciences : an official journal of the Society of Toxicology2017
From the Cover: Three-Dimensional (3D) HepaRG Spheroid Model With Physiologically Relevant Xenobiotic Metabolism Competence and Hepatocyte Functionality for Liver Toxicity Screening.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
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
46 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
- SINEUP-mediated enhancement of HNF4α improves metabolic function in Huh7-based bioengineered hepatic microtissues.Journal of liver cancer · 2026Article
- Exploring the potential of liver microphysiological systems of varied configurations to model cholestatic chemical effects.Archives of toxicology · 2026Article
- Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Transferability and Reproducibility of the HepaRG CometChip Assay.Environmental and molecular mutagenesis · 2025Article
- Establishing scientific confidence in a two-chamber co-culture system to evaluate androgenic response in the presence of hepatic metabolism.Toxicology letters · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Article
- HepaRGNAM journal · 2025Article
- Alternatives to animal-derived extracellular matrix hydrogels? An explorative study with HepaRG cells in animal-free hydrogels under static and dynamic culture conditions.Frontiers in toxicology · 2025Article
- Time-course characterization of whole-transcriptome dynamics of HepG2/C3A spheroids and its toxicological implications.Toxicology letters · 2024Article
- Improved functionality of hepatic spheroids cultured in acoustic levitation compared to existing 2D and 3D models.Scientific reports · 2024Article
- Hepatic spheroid-on-a-chip: Fabrication and characterization of a spheroid-basedBiomicrofluidics · 2024Article
- Novel Strategy to Assess the Neurotoxicity of Organic Solvents Such as Glycol Ethers: Protocol for Combining In Vitro and In Silico Methods With Human-Controlled Exposure Experiments.JMIR research protocols · 2024Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
- Review
- Analysis of reproducibility and robustness of OrganoPlate® 2-lane 96, a liver microphysiological system for studies of pharmacokinetics and toxicological assessment of drugs.Toxicology in vitro : an international journal published in association with BIBRA · 2022Article
- Specific Gene Duplication and Loss of Cytochrome P450 in Families 1-3 in Carnivora (Mammalia, Laurasiatheria).Animals : an open access journal from MDPI · 2022Article
- Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages.Toxicology in vitro : an international journal published in association with BIBRA · 2022Review
- Towards better prediction of xenobiotic genotoxicity: CometChip technology coupled with a 3D model of HepaRG human liver cells.Archives of toxicology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using invitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5). This invitro model maintains a stable phenotype over multiple weeks in both 96- and 384-well formats, supports highly reproducible tissue-like architectures and models pharmacologically- and environmentally important hepatic receptor pathways (ie AhR, CAR, and PXR) analogous to primary human hepatocyte cultures. HepaRG spheroid cultures use 50-100× fewer cells than conventional two dimensional cultures, and enable the identification of metabolically activated toxicants. Spheroid size, time in culture and culture media composition were important factors affecting basal levels of xenobiotic metabolism and liver enzyme inducibility with activators of hepatic receptors AhR, CAR and PXR. Repeated exposure studies showed higher sensitivity than traditional 2D cultures in identifying compounds that cause liver injury and metabolism-dependent toxicity. This platform combines the well-documented impact of 3D culture configuration for improved tissue functionality and longevity with the requisite throughput and repeatability needed for year-over-year toxicology screening.
Indexed as
Identifiers
What OpenQuestion holds
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.