[Growth and differentiation of neonatal rat hepatocytes in primary culture]

Liver plays a central role in metabolism of the body and it regenerates actively after injury. Primary cultured hepatocytes are suitable for studies on its growth and complex functions, because these cells mimic many liver functions and respond well to various hormones just like hepatocytes in vivo. Adult hepatocytes in culture are quiescent, but they proliferate in the presence of appropriate mitogens. Rat platelets contain a hepatocyte growth factor (HGF) and growth inhibitors. This HGF was found to be a labile protein of 100 kDa consisting of subunits of 34 and 69 kDa. One inhibitory factor, identified as transforming growth factor (TGF)-beta, shown to be released from platelets in a latent form and to be activated by its dissociation from bound masking proteins. Interleukin (IL)-1 and -6 also inhibit growth of hepatocytes. Besides these humoral factors, we found that the cell density in culture is an important regulatory factor for hepatocyte growth; a high cell density suppresses cell growth and promotes expression of differentiated liver functions. The roles of these humoral and membranous factors in the mechanism of liver regeneration are discussed. In contrast, neonatal hepatocytes in culture can grow autonomously without an added mitogen and they secrete several growth factors into the medium. This autocrine growth ceases rapidly after birth and differentiated characters appear in neonatal hepatocytes in culture. This change from growth to differentiation of immature hepatocytes can be stimulated by contact of the cells with adult hepatocytes. Therefore, micro-architecture of surroundings of hepatocytes is very important for regulation of liver functions and growth of not only adult hepatocytes, but also neonatal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)