Cited by 136Drug-Induced Hepatotoxicity and ProtectionLiver physiology and pathologyOrgan Transplantation Techniques and Outcomes

GENE EXPRESSION IN HUMAN HEPATOCYTES IN SUSPENSION AFTER ISOLATION IS SIMILAR TO THE LIVER OF ORIGIN, IS NOT AFFECTED BY HEPATOCYTE COLD STORAGE AND CRYOPRESERVATION, BUT IS STRONGLY CHANGED AFTER HEPATOCYTE PLATING

Richert, Lysiane, Liguori, Michael J., Abadie, Catherine, Heyd, Bruno, Mantion, Georges, Halkic, Nermin, Waring, Jeffrey F.·2006·Drug Metabolism and Disposition

Abstract

Isolated primary human hepatocytes are a well accepted system for evaluating pharmacological and toxicological effects in humans. However, questions remain regarding how culturing affects the liver-specific functions of the hepatocytes. In addition, cryopreservation could also potentially affect the differentiation state of the hepatocytes. The first aim of the present study was to compare gene expression in freshly isolated primary hepatocytes to that of the liver of origin and to evaluate the expression changes occurring after cryopreservation/thawing, both when maintained in suspension and after plating. The second aim of the present study was to evaluate gene expression in hepatocytes after cold storage of suspensions up to 24 h compared with freshly isolated hepatocytes in suspension. Our results show that the gene expression in freshly isolated human hepatocytes in suspension after isolation is similar to that of the liver of origin. Furthermore, gene expression in primary human hepatocytes in suspension is not affected by hepatocyte cold storage and cryopreservation. However, the gene expression is profoundly affected in monolayer cultures after plating. Specifically, gene expression changes were observed in cultured relative to suspensions of human hepatocytes that are involved in cellular processes such as phase I/II metabolism, basolateral and canalicular transport systems, fatty acid and lipid metabolism, apoptosis, and proteasomal protein recycling. An oxidative s…

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Crossref · 10.1124/dmd.105.007708

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Authors
Richert, L., Liguori, M. J., Abadie, C., Heyd, B., Mantion, G., Halkic, N., & Waring, J. F.
Affiliations
Université de Franche-Comté (FR)
Venue
Drug Metabolism and Disposition
Publisher
Elsevier BV
Published
2006-05
Volume
34
Issue
5
Pages
870-879
ISSN
0090-9556 (ISSN-L)
OpenAlex
W2130093373
Cited by
136
References
42
Citations by year
2026: 2 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 6 · 2021: 13 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 10 · 2014: 4 · 2013: 9 · 2012: 11
FWCI
6.08
Type
journal article
Language
en
Open access
closed
Locations
  • Drug Metabolism and Disposition (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
primary human hepatocytes, gene expression, hepatocyte cryopreservation, cold storage, monolayer culture, hepatocyte differentiation, phase I and II metabolism, apoptosis, oxidative stress response
MeSH terms
Cell Separation, Cells, Cultured, Cytological Techniques, Humans, Liver, RNA, Tissue Preservation, Gene Expression, Cryopreservation, Oligonucleotide Array Sequence Analysis, Hepatocytes, In Vitro Techniques

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