Maturation of the Extracellular Matrix and Cell Adhesion Molecules in Layered Co-cultures of HepG2 and Endothelial Cells
Source: The Journal of Biochemistry, Volume 145, Number 5, 27 May 2009 , pp. 591-597(7)
Publisher: Oxford University Press
Abstract:We previously reported that using thermo-responsive culture surfaces, a layered co-culture was achieved by placing an endothelial cell sheet onto a layer of human hepatoma cell line HepG2 in order to develop a culture model that mimics hepatic lobules. In the layered co-culture cells, the expression levels of liver-specific genes gradually increased. A cross-sectional view of the layered co-culture cells showed that the thickness of the layer slowly increased after layering, as did extracellular matrix (ECM) deposition around HepG2 cells. In this study, we report that the molecular compositions of ECM and cell-adhesion molecules changed in the layered co-culture cells. Gene expression of integrin α4 and decorin gradually increased after layering, and the time-course pattern of these genes was correlated with that of liver-specific genes. Moreover, the layered co-culture system has the ability to assemble a branching network of fibronectin fibrils. These results suggest that a vastly different extracellular environment in layered co-culture cells may induce an increase in liver-specific functions.
Document Type: Regular Paper
Affiliations: 1: Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo 204-8588; and , 2: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo 162-8666, Japan, 3: Advanced Medical Materials Group, Biomaterials Center, National Institute for Materials Science, 1-1, Namiki, Tsukuba, Ibaraki 305-0044; ,
Publication date: 27 May 2009