Established mouse liver cell lines as a model system for studying epithelio-mesenchymal interactions in morphogenesis

Four cell lines were established from both fetal and adult livers of mice (ddY strain) by colony isolation methods, and these were characterized by morphological, immunological and biochemical examination. An epithelial cell line from a fetus (eE1-10) was identified to be derived from the biliary tract epithelium. Another epithelial cell line from an adult (aE3) reconstructed bile canaliculi-like structures in aggregates and secreted several serum proteins, indicating that it was derived from the hepatic parenchyma. The other two lines (eF1 and aF1) are fibroblastic in morphology. These were derived from fetal and adult livers, respectively. Both eE1-10 and the fetal fibroblastic cell line (eF1) are hypotetraploid, whereas both aE3 and the adult fibroblastic cell line (aF1) are hypodiploid. All four cell lines showed both contact inhibition and anchorage dependency of growth. Luminal structures with basal laminar, similar to bile ducts, were reconstituted from eE1-10 cells when co-aggregated with aF1 fibroblastic cells. Luminal structures were also formed from eE1-10 cells embedded in collagen gel. These, however, had no basal lamina and there was less development of microvilli than in aggregates mixed with fibroblastic cells. These results indicate that the fibroblastic cells afford favourable conditions for maintenance of the elaborated luminal structure of epithelial cells through production of the basal lamina.