Evidence map›Paper›PMID 36677681›Full record

ArticleMolecules (Basel, Switzerland)2023

Drug Metabolism of Hepatocyte-like Organoids and Their Applicability in In Vitro Toxicity Testing.

Manon C Bouwmeester, Yu Tao, Susana Proença, Frank G van Steenbeek, Roos-Anne Samsom, Sandra M Nijmeijer, Theo Sinnige, Luc J W van der Laan, Juliette Legler, Kerstin Schneeberger and 2 more

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Cholangiocyte organoids to study drug-induced injury.Stem cell research & therapy · 2024
    Article
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Manon C BouwmeesterDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands.ORCID 0000-0002-7141-9939
Yu TaoDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands.
Susana ProençaDivision of Toxicology, Wageningen University, 6700 EA Wageningen, The Netherlands.ORCID 0000-0003-1544-4686
Frank G van SteenbeekDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands.ORCID 0000-0001-5460-6540
Roos-Anne SamsomDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands.
Sandra M NijmeijerInstitute for Risk Assessment Sciences, Utrecht University, 3584 CM Utrecht, The Netherlands.
Theo SinnigeInstitute for Risk Assessment Sciences, Utrecht University, 3584 CM Utrecht, The Netherlands.
Luc J W van der LaanDepartment of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, 3015 CN Rotterdam, The Netherlands.ORCID 0000-0002-0651-5334
Juliette LeglerInstitute for Risk Assessment Sciences, Utrecht University, 3584 CM Utrecht, The Netherlands.ORCID 0000-0001-6321-1567
Kerstin SchneebergerDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands.ORCID 0000-0001-8109-7657
Nynke I KramerDivision of Toxicology, Wageningen University, 6700 EA Wageningen, The Netherlands.ORCID 0000-0002-3281-1815
Bart SpeeDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, 3584 CT Utrecht, The Netherlands.ORCID 0000-0002-8114-0560
Utrecht University · NLErasmus MC · NL

Funding

Dutch Research Council 15498
6 · The paper itself

Abstract

Emerging advances in the field of in vitro toxicity testing attempt to meet the need for reliable human-based safety assessment in drug development. Intrahepatic cholangiocyte organoids (ICOs) are described as a donor-derived in vitro model for disease modelling and regenerative medicine. Here, we explored the potential of hepatocyte-like ICOs (HL-ICOs) in in vitro toxicity testing by exploring the expression and activity of genes involved in drug metabolism, a key determinant in drug-induced toxicity, and the exposure of HL-ICOs to well-known hepatotoxicants. The current state of drug metabolism in HL-ICOs showed levels comparable to those of PHHs and HepaRGs for CYP3A4; however, other enzymes, such as CYP2B6 and CYP2D6, were expressed at lower levels. Additionally, EC50 values were determined in HL-ICOs for acetaminophen (24.0−26.8 mM), diclofenac (475.5−>500 µM), perhexiline (9.7−>31.5 µM), troglitazone (23.1−90.8 µM), and valproic acid (>10 mM). Exposure to the hepatotoxicants showed EC50s in HL-ICOs comparable to those in PHHs and HepaRGs; however, for acetaminophen exposure, HL-ICOs were less sensitive. Further elucidation of enzyme and transporter activity in drug metabolism in HL-ICOs and exposure to a more extensive compound set are needed to accurately define the potential of HL-ICOs in in vitro toxicity testing.

Indexed as

AcetaminophenHepatocytesOrganoidsCytochrome P-450 CYP3AHumansLiverToxicity TestsAcetaminophenCytochrome P-450 CYP3Adrug-induced liver injuryhepatic in vitro modelhepatocyte-like cellshepatotoxicityintrahepatic cholangiocyte organoids

Identifiers

PMID36677681
PMCPMC9867526
OpenAlexW4313891864

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.