Development of a hybrid artificial liver support system and its application to hepatic failure animals

We found that primary rat, dog and porcine hepatocytes form multicellular aggregates (spheroids) in the pores of polyurethane foam (PUF) as a culture substratum, and that they maintain several liver-specific functions, such as albumin secretion and urea synthesis, for at least 2 weeks in vitro. Using these spheroids in PUF, we developed a hybrid artificial liver support system (HALSS), that induces an extracorporeal circulation system, and a hepatocyte culture module. The geometry of the module was a packed bed whose total volume was filled with a PUF block with many capillaries supplying the medium. About 10% of the hepatocytes in a whole liver were inoculated into the PUF pores and formed spheroids. This HALSS was applied to various animals with hepatic failure. In the experiment with rats induced with D-galactosamine, 80% of rats with hepatic failure recovered by applying HALSS including a module packed with 5.0 x 10(7) cells (n 5). Furthermore, in large animal experiments, using dogs (15 kg) and pigs (25 kg) with ischemic liver failure, the blood glucose concentrations were well maintained and the increases in blood ammonia concentration were suppressed by applying the HALSS including the modules packed with 3.0 x 10(9) hepatocytes for dog and 6.4 x 10(9) hepatocytes for pig. These results indicate that HALSS seems promising for clinical application.