ReviewEuropean journal of drug metabolism and pharmacokinetics2019
Advanced In Vitro HepaRG Culture Systems for Xenobiotic Metabolism and Toxicity Characterization.
Review in European journal of drug metabolism and pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Comparative case study on NAMs: towards enhancing specific target organ toxicity analysis.Archives of toxicology · 2024Article
- Effects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells.Experimental and therapeutic medicine · 2024Article
- Perspective of 3D culture in medicine: transforming disease research and therapeutic applications.Frontiers in bioengineering and biotechnology · 2024Review
- Comparison of in vitro approaches for predicting the metabolism of the selective androgen receptor modulator RAD140.Analytical and bioanalytical chemistry · 2023Article
- Engineered human liver based on pullulan-dextran hydrogel promotes mice survival after liver failure.Materials today. Bio · 2023Article
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- Effects ofPharmaceutics · 2021Article
- 3,3'-Dichlorobiphenyl Is Metabolized to a Complex Mixture of Oxidative Metabolites, Including Novel Methoxylated Metabolites, by HepG2 Cells.Environmental science & technology · 2020Article
- Population Pharmacokinetics of Mycophenolic Acid Co-Administered with Tacrolimus in Corticosteroid-Free Adult Kidney Transplant Patients.Clinical pharmacokinetics · 2019Observational
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several HepaRG three-dimensional (3D) in vitro model systems have been developed to improve the predictability of xenobiotic metabolism and toxicity. In this review, we present a detailed summary and critique of the performance of various HepaRG 3D models compared to the conventional 2D monolayer culture. HepaRG 3D models can be broadly categorized into (1) scaffold-free, (2) scaffold-based, and (3) bioartificial liver (BAL) models. With respect to the scaffold-free configurations, the hanging drop model closely mimics the normal physiological function and metabolic profile of the liver. The micromold model is suitable for high-throughput multiplexed assays and exhibits higher accuracy when predicting drug-induced liver toxicity risk in both acute and chronic culture. Scaffold- and BAL-based models also present improved precision and accuracy for hepatotoxic drug screening in addition to allowing improved model control to closely mimic physiological assay conditions. Overall, all 3D HepaRG models exhibit improved cellular function, metabolic activity, and toxicity screening ability compared to the conventional 2D monolayer culture. These improvements reported in 3D models may be due to a higher degree of differentiation and cell polarity. Nevertheless, the expression and functions of various phase II, phase III, and nuclear receptors need to be further characterized in these 3D models.
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Registered trials
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