Journal
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
Volume 111, Issue 1, Pages 78-84Publisher
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2010.08.008
Keywords
HepG2 cells; Hepatocyte; Three-dimension culture; Micro-space cell culture; Hepatocyte-specific function; Drug toxicity
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labor, and Welfare of Japan
- Japan Health Science Foundation
- Ministry of Human Health and Welfare of Japan
- Human Science Foundation
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A micro-space cell culture system was recently developed in which cells such as hepatocytes can be cultured and formed into a multicellular three-dimensional (3D) architecture. In this study, we assessed the performance of HepG2 cells cultured in this micro-space cell culture system in a drug toxicity test, and evaluated the effects of micro-space culture on their hepatocyte-specific functions. The micro-space cell culture facilitated the formation of 3D HepG2 cell architecture. HepG2 cells cultured in a micro-space culture plate exhibited increased albumin secretion and enhanced mRNA expression levels of cytochrome P450 (CYP) enzyme compared to those cultured in a monolayer culture. When the cells were exposed to acetaminophen, a hepatotoxic drug, the damage to the HepG2 cells grown in micro-space culture was greater than the damage to the HepG2 cells grown in monolayer culture. In addition, human primary hepatocytes grown in micro-space culture also exhibited increased albumin secretion, enhanced CYP mRNA expression levels and increased sensitivity to acetaminophen compared to those grown in monolayer culture. These results suggest that this micro-space culture method enhances the hepatocyte-specific functions of hepatocytes, including drug-metabolizing enzyme activities, making hepatocytes grown in the micro-space culture system a useful tool for evaluating drug toxicity in vitro. (C) 2010, The Society for Biotechnology, Japan. All rights reserved.
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