Cited by 292Liver physiology and pathologyDrug-Induced Hepatotoxicity and ProtectionOrgan Transplantation Techniques and Outcomes

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Molecular Mechanisms Underlying the Dedifferentiation Process of Isolated Hepatocytes and Their Cultures

Elaut, Greetje, Henkens, Tom, Papeleu, Peggy, Snykers, Sarah, Vinken, Mathieu, Vanhaecke, Tamara, Rogiers, Vera·2006·Current Drug Metabolism

DOI 10.2174/138920006778017759

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Abstract

Primary hepatocytes and their cultures are a simple but versatile, well-controlled, and relatively easy to handle in vitro system that is well-accepted for investigating xenobiotic biotransformation, enzyme induction and inhibition, and (biotransformation-mediated) hepatotoxicity. In addition, hepatocyte cultures have proven to be valuable tools in the study of liver physiology, viral hepatitis, and liver regeneration and are proposed as an alternative to orthotopic liver transplantation. It has been observed, however, that a number of liver-specific functions are progressively lost with time when hepatocytes are isolated and cultivated. These phenotypic changes are primarily the result of fundamental changes in gene expression concomitant with a diminished transcription of the relevant liver-specific genes, and can be interpreted as a 'dedifferentiation' of the isolated hepatocytes. Ischemia-reperfusion stress induced during the isolation process, disruption of the normal tissue architecture, as well as an adaptation to the in vitro environment are underlying factors and will be extensively discussed. A detailed description of the regulation of the hepatocyte phenotype in vivo in the first section of this review will help to understand the effect of these factors on hepatocyte gene expression. Although different approaches, mainly mimicking the in vivo hepatocyte environment, have been succesfully used to prevent or slow down the dedifferentiation of primary hepatocytes in m…

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Authors: Elaut, G., Henkens, T., Papeleu, P., Snykers, S., Vinken, M., Vanhaecke, T., & Rogiers, V.
Affiliations: Vrije Universiteit Brussel (BE)
ORCID: Vinken, Mathieu
Vanhaecke, Tamara
Rogiers, Vera
Venue: Current Drug Metabolism
Publisher: Bentham Science Publishers Ltd.
Published: 2006-08-01
Volume: 7
Issue: 6
Pages: 629-660
ISSN: 1389-2002 (ISSN-L)
DOI: 10.2174/138920006778017759
OpenAlex: W2150031244
Cited by: 292
References: 0
Citations by year: 2026: 8 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 18 · 2021: 26 · 2020: 20 · 2019: 16 · 2018: 21 · 2017: 16 · 2016: 16 · 2015: 13 · 2014: 14 · 2013: 17 · 2012: 16
FWCI: 9.68
Type: journal article
Language: en
Open access: closed
Locations: Current Drug Metabolism (publishedVersion)
PubMed (publishedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Topics: Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords: hepatocyte dedifferentiation, primary hepatocytes, hepatocyte culture, hepatocyte phenotype, gene expression, hepatocyte isolation, hepatocyte-like cells, hepatic progenitor cells, xenobiotic metabolism, liver regeneration
MeSH terms: Animals, Cell Communication, Cell Differentiation, Cells, Cultured, Extracellular Matrix, Gene Expression Regulation, Humans, Nitric Oxide, Phenotype, Eicosanoids, Cytokines, Apoptosis, Reactive Oxygen Species, Hepatocytes, Reactive Nitrogen Species, Cell Proliferation

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Molecular Mechanisms Underlying the Dedifferentiation Process of Isolated Hepatocytes and Their Cultures

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