Hepatocyte proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix.

Abstract

The culture conditions found to result in stable proliferation of normal rat hepatocytes are: subconfluent cell densities; serum-free medium; hormonally defined medium containing epidermal growth factor, insulin, glucagon, prolactin and other growth factors; and substrata of liver extracellular matrix depleted of growth inhibitors. Serum was found deleterious to parenchymal cells: it was inhibitory to the expression of liver-specific functions, cytostatic to parenchymal cells at all seeding densities, and cytotoxic to them at low seeding densities. These studies emphasize the relevance of synergies in the influences of hormones and extracellular matrix in regulating hepatocellular physiology.