Enhancement of Hepatocyte Function Through Heterotypic Cell-Cell Interactions Using E-Cadherin-Expressing NIH3T3 Cells

Abstract

Heterotypic cell-cell interactions between parenchymal and nonparenchymal cells play crucial roles in liver, and these interactions have to be taken into account in replicating tissue functions in bioartificial liver and in liver tissue engineering. The calcium-dependent, transmembrane molecules, cadherins directly regulate morphologic events. The predominant cadherin of hepatocytes is E-cadherin. Because cadherin is a homophilic adhesion molecule, cells expressing different cadherin molecules tend to distinguish between each other when artificially mixed in vitro. In the present study, in order to engineer heterotypic interactions between hepatocytes and mesenchymal cells via E-cadherin molecules, the E-cadherin gene was introduced into mouse fibroblast NIH3T3 cells, and the effects of co-culture of E-cadherin-expressing NIH3T3 cells with hepatocytes were investigated. NIH3T3 cells were transfected with the plasmid encoding an expression cassette of full-length murine E-cadherin cDNA, and stable E-cadherin-expressing clones were established. Thus, E-cadherin was expressed in NIH3T3 fibroblasts, and cell-cell interactions between hepatocytes and fibroblasts were artificially engineered. When the E-cadherin-expressing NIH3T3 cells were co-cultured with rat hepatocytes, the cell-cell contacts were formed with high frequency, and enhanced albumin secretion was observed. These results indicate that E-cadherin-expressing NIH3T3 cells may be useful for co-culture-based bioartificial liver and liver tissue engineering.