ArticleArchives of toxicology2026
Exploring the potential of liver microphysiological systems of varied configurations to model cholestatic chemical effects.
Article in Archives of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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.
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Who cites it
4 citing papers in PubMed.
- Introduction to the 3RsC's cross-platform microphysiological systems evaluation for drug-induced liver injury in collaboration with FDA-CDER.Regulatory toxicology and pharmacology : RTP · 2026Article
- Chemical Distribution Kinetics of Five Polycyclic Aromatic Hydrocarbons in a Microphysiological System.Toxics · 2026Article
- Lentiviral-mediated expression of cytochrome P450 2D6 in HepaRG cells: new means for in vitro xenobiotic biotransformation and cellular response to chimeric viral mRNA.Archives of toxicology · 2026Article
- New Frontiers of Drug Development Through the Use of New Approach Methodologies.The AAPS journal · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Human in vitro liver tissue models have evolved to maintain hallmarks of hepatocellular function for extended periods with potential to model aspects of cholestasis for drug and chemical safety applications. Microphysiological systems (MPS) have been suggested as promising new approaches to model liver physiology and predict chemical-induced cholestasis in humans. This study comprehensively compared both basal function and toxicant-induced effects in 2D cultures and three liver MPS (i.e., 2-lane OrganoPlate, 3-lane OrganoPlate and PhysioMimix LC12) that were seeded with either HepaRG cells, primary human hepatocytes (PHH), or human induced pluripotent stem cell (iPSC)-derived hepatocytes. PHH and iPSC-derived hepatocytes (iHeps) were tested up to 7 days while HepaRG were evaluated over 30 days. Albumin, urea, CYP3A4 activity, and bile acids were measured. HepaRG and PHH showed comparable function in 2D and PhysioMimix LC12, with albumin higher for HepaRG and urea higher for PHH. HepaRG maintained production of biomarkers for up to 30 days in both 2D and PhysioMimix LC12. In both OrganoPlate models, HepaRG produced higher levels of albumin and urea as compared to iHeps; still, HepaRG function in OrganoPlate was lower than that in 2D or PhysioMimix LC12. Bile acid synthesis (after 7 days) was much higher with PHH in the PhysioMimix LC12 as compared to 2D PHH or 2D HepaRG. Upon exposure to cholestatic agents (bosentan, 2-octynoic acid, α-naphthyl isocyanate), robust CYP3A4 induction was observed in HepaRG and PHH treated with bosentan and α-naphthylisocyanate. Only in PhysioMimix LC12, both HepaRG and PHH, all compounds elicited decreased bile acid release into cell culture medium, a biomarker for cholestasis. In summary, the hepatocyte functional markers (CYP3A4, albumin, urea) were comparable between PHH and HepaRG in 2D and PhysioMimix LC12 MPS. However, the effects of cholestatic agents on PHH and HepaRG, specifically, bile acid release were detected only in the PhysioMimix LC12 with PHH showing more consistent responses compared to HepaRG.
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Registered trials
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