Evidence map›Paper›PMID 34762139›Full record

ArticleArchives of toxicology2022

DMSO-free highly differentiated HepaRG spheroids for chronic toxicity, liver functions and genotoxicity studies.

Sophie Rose, Marie Cuvellier, Frédéric Ezan, Jennifer Carteret, Arnaud Bruyère, Vincent Legagneux, Fabrice Nesslany, Georges Baffet, Sophie Langouët

Abstract read
PubMed Publisher
In one paragraph

Article in Archives of toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.2field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Application of the Comet Assay in Advanced In Vitro Models.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. In Vitro Models for Studying Chronic Drug-Induced Liver Injury.International journal of molecular sciences · 2022
    Review
  20. 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

9 authors at 2 institutions in 1 country.

Sophie RoseUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France.ORCID 0000-0001-8537-8691
Marie Cuvellier *Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France.
Frédéric Ezan *Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France.
Jennifer CarteretUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France.
Arnaud BruyèreUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France.
Vincent LegagneuxUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France.
Fabrice NesslanyGenotoxicology Department, Institut Pasteur de Lille, 1, Rue du Professeur Calmette, 59000, Lille, France.
Georges Baffet *Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France. georges.baffet@univ-rennes1.fr.
Sophie Langouët *Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, 35000, Rennes, France. sophie.langouet@univ-rennes1.fr.ORCID 0000-0002-0016-5425
Inserm · FRUniversité de Lille · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The liver is essential in the elimination of environmental and food contaminants. Given the interspecies differences between rodents and humans, the development of relevant in vitro human models is crucial to investigate liver functions and toxicity in cells that better reflect pathophysiological processes. Classically, the differentiation of the hepatic HepaRG cell line requires high concentration of dimethyl sulfoxide (DMSO), which restricts its usefulness for drug-metabolism studies. Herein, we describe undifferentiated HepaRG cells embedded in a collagen matrix in DMSO-free conditions that rapidly organize into polarized hollow spheroids of differentiated hepatocyte-like cells (Hepoid-HepaRG). Our conditions allow concomitant proliferation with high levels of liver-specific functions and xenobiotic metabolism enzymes expression and activities after a few days of culture and for at least 4 weeks. By studying the toxicity of well-known injury-inducing drugs by treating cells with 1- to 100-fold of their plasmatic concentrations, we showed appropriate responses and demonstrate the sensitivity to drugs known to induce various degrees of liver injury. Our results also demonstrated that the model is well suited to estimate cholestasis and steatosis effects of drugs following chronic treatment. Additionally, DNA alterations caused by four genotoxic compounds (Aflatoxin B

Indexed as

Dimethyl SulfoxideHepatocytesDNA DamageLiverMicronucleus TestsDimethyl Sulfoxide3D culture modelGenotoxicityHepaRG cellsHuman liver injuryLong-term differentiationToxicity screening

Identifiers

PMID34762139
OpenAlexW3213300456

What OpenQuestion holds

Textmetadata
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.