Modulation of human fetal hepatocyte survival and differentiation by interactions with a rat liver epithelial cell...

Fetal human hepatocytes were isolated by collagenase digestion of liver fragments and cultured either alone or mixed with rat liver epithelial cells. Whereas they did not survive more than 2-3 weeks and showed rapid morphologic and functional alterations in conventional culture, fetal hepatocytes survived and retained or reverted to a globular morphology for several weeks and showed active albumin secretion for at least 13 days when cultured with rat liver cells. Increased levels of secreted albumin correlated with deposition of an insoluble extracellular material containing fibronectin and type III collagen located principally between the two cell types and around parenchymal cells. These observations show that fetal human hepatocytes are able to interact in vitro with another epithelial liver cell type obtained from a divergent species and that these cell-cell interactions influence both hepatocyte survival and expression of albumin.