Document Detail


Hepatocyte differentiation.
MedLine Citation:
PMID:  20645049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increasingly, research suggests that for certain systems, animal models are insufficient for human toxicology testing. The development of robust, in vitro models of human toxicity is required to decrease our dependence on potentially misleading in vivo animal studies. A critical development in human toxicology testing is the use of human primary hepatocytes to model processes that occur in the intact liver. However, in order to serve as an appropriate model, primary hepatocytes must be maintained in such a way that they persist in their differentiated state. While many hepatocyte culture methods exist, the two-dimensional collagen "sandwich" system combined with a serum-free medium, supplemented with physiological glucocorticoid concentrations, appears to robustly maintain hepatocyte character. Studies in rat and human hepatocytes have shown that when cultured under these conditions, hepatocytes maintain many markers of differentiation including morphology, expression of plasma proteins, hepatic nuclear factors, phase I and II metabolic enzymes. Functionally, these culture conditions also preserve hepatic stress response pathways, such as the SAPK and MAPK pathways, as well as prototypical xenobiotic induction responses. This chapter will briefly review culture methodologies but will primarily focus on hallmark hepatocyte structural, expression and functional markers that characterize the differentiation status of the hepatocyte.
Authors:
Katy M Olsavsky Goyak; Elizabeth M Laurenzana; Curtis J Omiecinski
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Methods in molecular biology (Clifton, N.J.)     Volume:  640     ISSN:  1940-6029     ISO Abbreviation:  Methods Mol. Biol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-10-28     Revised Date:  2014-03-31    
Medline Journal Info:
Nlm Unique ID:  9214969     Medline TA:  Methods Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  115-38     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bioreactors
Cell Culture Techniques / instrumentation,  methods
Cell Differentiation*
Cells, Cultured
Cytochrome P-450 Enzyme System / metabolism
Equipment Design
Hepatocyte Nuclear Factors / metabolism
Hepatocytes / cytology*,  drug effects,  metabolism
Humans
Hypnotics and Sedatives / pharmacology
Phenobarbital / pharmacology
Rats
Xenobiotics / metabolism
Grant Support
ID/Acronym/Agency:
R01 GM066411/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Hepatocyte Nuclear Factors; 0/Hypnotics and Sedatives; 0/Xenobiotics; 9035-51-2/Cytochrome P-450 Enzyme System; YQE403BP4D/Phenobarbital

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