A Comparative Study of Genome-Wide Transcriptional Profiles of Primary Hepatocytes in Collagen Sandwich and Monolayer Cultures

Two commonly used culture systems in hepatic tissue engineering are the collagen sandwich (CS) and monolayers of cells. In this study, genome-wide gene expression profiles of primary hepatocytes were measured over an 8-day period for each cell culture system using Affymetrix GeneChips and compared v...

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Bibliographic Details
Published in:Tissue engineering. Part C, Methods Methods, 2010-12, Vol.16 (6), p.1449-1460
Main Authors: Kim, Yeonhee, Lasher, Christopher D., Milford, Logan M., Murali, T.M., Rajagopalan, Padmavathy
Format: Article
Language:English
Subjects:
Animals
Cell culture
Cell Culture Techniques - instrumentation
Cell Culture Techniques - methods
Cells, Cultured
Chemical properties
Collagen
Collagen - chemistry
Collagen - pharmacology
Comparative studies
Female
Gene Expression Profiling
Gene Expression Regulation
Genetic aspects
Genetic transcription
Genome - physiology
Genomics
Growth
Health aspects
Hepatocytes - cytology
Hepatocytes - metabolism
Hepatology
Liver cells
Oligonucleotide Array Sequence Analysis
Physiological aspects
Rats
Rats, Inbred Lew
Tissue Scaffolds - chemistry
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Summary:Two commonly used culture systems in hepatic tissue engineering are the collagen sandwich (CS) and monolayers of cells. In this study, genome-wide gene expression profiles of primary hepatocytes were measured over an 8-day period for each cell culture system using Affymetrix GeneChips and compared via gene set enrichment analysis to elicit biologically meaningful information at the level of gene sets. Our results demonstrate that gene expression in hepatocytes in CS cultures steadily and comprehensively diverges from that in monolayer cultures. Gene sets up-regulated in CS cultures include several associated with liver metabolic and synthesis functions, such as metabolism of lipids, amino acids, carbohydrates, and alcohol, and synthesis of bile acids. Monooxygenases such as Cytochrome-P450 enzymes do not show any change between the culture systems after 1 day, but exhibit significant up-regulation in CS cultures after 3 days in comparison to hepatocyte monolayers. These data provide insights into the up- and down-regulation of several liver-critical gene sets and their subsequent effects on liver-specific functions. These results provide a baseline for further explorations into the systems biology of engineered liver mimics.
ISSN:1937-3384
1937-3392
DOI:10.1089/ten.tec.2010.0012