ArticleInternational journal of molecular sciences2016
In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- An Exploratory Study on the Pathogenic Role of Faecal Extracellular Vesicles in Metabolic Dysfunction-Associated Steatotic Liver Disease Progression and in Drug-Induced Liver Injury.Journal of extracellular vesicles · 2026Article
- Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening.Archives of toxicology · 2025Article
- Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies.Frontiers in cell and developmental biology · 2021Review
- Effect of inoculum density on human-induced pluripotent stem cell expansion in 3D bioreactors.Cell proliferation · 2019Article
- Metabolism of remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system.Drug design, development and therapy · 2019Article
- Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.Bioengineering (Basel, Switzerland) · 2018Article
- Hepatic differentiation of human iPSCs in different 3D models: A comparative study.International journal of molecular medicine · 2017Article
- In vivo-like 3-D model for sodium nitrite- and acrylamide-induced hepatotoxicity tests utilizing HepG2 cells entrapped in micro-hollow fibers.Scientific reports · 2017Article
- Integrated Assessment of Diclofenac Biotransformation, Pharmacokinetics, and Omics-Based Toxicity in a Three-Dimensional Human Liver-Immunocompetent Coculture System.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Research Advances on Hepatotoxicity of Herbal Medicines in China.BioMed research international · 2016Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro.
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