A preview of the practical application of hybrid artificial liver

: In order to replace the liver function, the development of the system where natural hepatocytes are immobilized in a matrix polymer might be considered as the best way. Each hepatocyte has a number of specific receptors for several ligards. We noticed that the hepatocyte recognizes the structure of oligosaccharides via asialoglycoprotein receptors and synthesizes lactose-carrying styrene polymer (PVLA) as a asialoglycoprotein model. On PVLA-coated dish, the specific functions as well as attachment of hepatocyte were successfully maintained. Moreover, cultured hepatocytes on PVLA substratum started gradual movement, and then remarkably formed multilayer aggregations which had long-term survival. Hepatocytes in the aggregation exhibited better maintenance of specific hepatocyte-functions such as the synthesis of albumin and secretion of bile acid, and retained mitochondrial enzyme activity than those in the monolayer culture on collagen and fibronectin. Furthermore, we found that DNA synthesis in cultured hepatocytes was correlated to the cell-shape which could be controlled by the concentration of PVLA substratum. These results also suggested that the PVLA could potentiate the regulation of the differentiation and proliferation of hepatocytes.