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Abstracts: ASAIO Bioengineering/tissue Engineering Abstracts

EXPRESSION OF CYP3A4 BY AN IMMORTALIZED HUMAN HEPATOCYTE LINE USING A RADIAL-FLOW BIOREACTOR

Akiyama, Ichiro1,2; Shimizu, Nobuyoshi2; Nagamori, Seishi3; Huh, Nam-ho1; Miyazaki, Masahiro1

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Cytochrome P450 (CYP) 3A is responsible for about 50% of drug metabolizing activity in the liver. The present study was undertaken to establish a CYP3A4-active model using radial-flow bioreactor (RFB) for in vitro analysis of human drug metabolism. The cells used were immortalized normal human fetal hepatocytes (OUMS-29) and its HNF4a-introduced subline (OUMS-29/H-11). It displays a number of liver functions and non-tumorigenecity. The cells were cultivated under high-density three-dimensional conditions in RFB. Number of OUMS-29 cells increased 15-fold over 49 days and their apical surfaces were covered with abundant microvilli, a characteristic of hepatocytes in vivo. Amount of albumin secreted by OUMS-29 cells in the three-dimensional RFB culture was 6-fold higher than those in a monolayer culture. CYP3A4 protein and an intermediate metabolite of testosterone by CYP3A4 were detected in OUMS-29/H11 cells cultivated in RFB longer than 29 days.

Conclusion:

These results indicate that the RFB culture of OUMS-29/H-11 cells is useful for screening and developing new drugs. This is the first report of an immortalized human hepatocytes culture using RFB.

Copyright © 2005 by the American Society for Artificial Internal Organs