OKANO Teruo    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Up-regulation of drug-metabolizing enzyme genes in layered co-culture of a human liver cell line and endothelial cells.
Journal	Formal name：Tissue engineering. Part A Abbreviation：Tissue Eng Part A ISSN code：(1937-3341)1937-3341(Linking)
Domestic / Foregin	Foregin
Volume, Issue, Page	14(11),pp.1861-9
Author and coauthor	Ohno Maki†, Motojima Kiyoto, Okano Teruo, Taniguchi Akiyoshi
Publication date	2008/10
Summary	Primary human hepatocytes are used extensively to study drug-metabolizing enzymes such as the cytochrome P450 (CYP) enzymes. However, the activities of these enzymes decrease rapidly during culture. In the present study, using a thermo-responsive culture dish, layered co-culture was achieved by placing a bovine pulmonary artery endothelial cell (BPAEC) sheet onto the human hepatoma cell line HepG2. In the BPAEC/HepG2 layered co-culture system, real-time polymerase chain reaction analysis showed that the expression levels of various CYP enzymes were more than 10 times greater 21 days after layering than with a HepG2 monolayer. The expression levels of CYP1B1, CYP2C9, CYP2E1, and CYP3A4 were up-regulated in a time-dependent manner, gradually increasing from day 10 after layering, and continuing to increase until at least day 21. The gene expression levels of the various CYP enzymes were almost identical to that of human liver. These results suggest that our layered co-culture system enhances the function of HepG2 cells and that our BPAEC/HepG2 layered co-culture system can serve as a useful model for the in vitro evaluation of CYP regulation.
DOI	10.1089/ten.tea.2007.0160
PMID	18847370