Fetal phenotypic expression by adult rat hepatocytes on collagen

Hepatocytes from adult rats were maintained in primary culture for up to 10-13 days on nylon meshes coated with a thin layer of rat tail collagen gel. Their ultrastructure closely resembled that of the liver parenchymal cell in vivo, but hepatocytes in late culture exhibited a pronounced buildup of microfilaments beneath their apical cell surface. Hepatocytes in earl and late cultures secreted albumin, transferrin, and a1-acid glycoprotein into the medium; they exhibited a 7- to 10-fold induction of tyrosine aminotransferase activity by dexamethasone; and they expressed an alkaline phosphatase that was similar to that of normal rat liver with respect to its inhibition by the liver enzyme inhibitor L-homoarginine. In addition, the hepatocytes in culture demonstrated phenot pic changes characteristic of fetal liver parenchymal cells. These changes, which paralleled an increase in DNA synthesis, in- cluded the expression of and linear increase in the activity of the fetal liver cell enzyme y-glutamyl transpeptidase, an in- creased production of a1-fetoprotein, and a change in the sub- strate specificity of fructose-bisphosphate aldolase to that of the fetal liver isozyme.