Maturation of the extracellular matrix and cell adhesion molecules in layered co-cultures of HepG2 and endothelial cells

Maki Ohno, Kiyoto Motojima, Teruo Okano, Akiyoshi Taniguchi

Research output: Contribution to journalArticle

27 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)591-597
Number of pages7
JournalJournal of biochemistry
Issue number5
Publication statusPublished - 2009 May 1



  • Cell-sheet technology
  • Co-culture
  • ECM
  • Gene expression
  • Hepatocyte

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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