Improvement of the performance of a packed-bed bioartificial liver

To construct a bioartificial liver, a culture technique to enable high-density and large-scale culture of hepatocytes so as to maintain viability and metabolic functions of cultured hepatocytes comparable to those in vivo is required. In order to achieve this goal the following attempts are under progress: Hepatocytes cultured in a packed-bed reactor (cell density: 8.6 x 10(6) cells/cm(3)-PVF), using reticulated polyvinyl formal (PVF) resin as a cell-supporting material, under high dissolved oxygen concentration ranging from 260 to 460 mu M showed 30% higher ammonium metabolic activity and 85% higher albumin secretion activity compared with those of the monolayer culture. Two kinds of nonparenchymal cells, i.e., nonparenchymal liver cells obtained from rats (NPC) and porcine aortic endothelial cells (EC), were adopted for coculture experiments using plate-shaped PVF resin. When hepatocytes were cocultured with NPC, no significant effects were observed. On the other hand, the hepatocytes cocultured with EC maintained longer albumin secretion than the hepatocytes cultured solely. Effects of shear stress ranging from 1 to 14 dyne/cm(2) on the coculture system of hepatocyte/NPC were investigated. Hepatocyte aggregates were formed and their aggregation was facilitated by exposure to shear flow Significant increases in metabolic functions were evoked by shear flow.