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Open Access Green as soon as Postprint is submitted to ZB.
Hepatocyte cell lines: their use, scope and limitations in drug metabolism studies.
Expert Opin. Drug Metab. Toxicol. 2, 183-212 (2006)
Gaining knowledge on the metabolism of a drug, the enzymes involved and its inhibition or induction potential is a necessary step in pharmaceutical development of new compounds. Primary human hepatocytes are considered a cellular model of reference, as they express the majority of drug-metabolising enzymes, respond to enzyme inducers and are capable of generating in vitro a metabolic profile similar to what is found in vivo. However, hepatocytes show phenotypic instability and have a restricted accessibility. Different alternatives have been explored in the past recent years to overcome the limitations of primary hepatocytes. These include immortalisation of adult or fetal human hepatic cells by means of transforming tumour virus genes, oncogenes, conditionally immortalised hepatocytes, and cell fusion. New strategies are currently being used to upregulate the expression of drug-metabolising enzymes in cell lines or to derive hepatocytes from progenitor cells. This paper reviews the features of liver-derived cell lines, their suitability for drug metabolism studies as well as the state-of-the-art of the strategies pursued in order to generate metabolically competent hepatic cell lines.
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Publication type
Article: Journal article
Document type
Review
ISSN (print) / ISBN
1742-5255
e-ISSN
1744-7607
Quellenangaben
Volume: 2,
Issue: 2,
Pages: 183-212
Publisher
Informa Healthcare
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Pioneer Campus (HPC)