Development of a hybrid artifical liver using PUF/three dimensional culture of normal hepatocytes

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1. We designed a prototype of hybrid artificial liver module using optimum polyurethane foam (PUF) material for spheroid formation of hepatocyte in vitro. The module was type of packed-bed with PUF plates (1.5X40X40mm) which immobilized spheroids. In serum-free medium supplemented with 1mM NH_4Cl as a toxic substance, this module detoxified ammonia and synthesized urea from ammonia. The urea synthesis rate of hepatocyte in the module was slightly higher than that of hepatocyte in vivo and was maintained for about 3 weeks.2. We also developed Multi-Capillary PUF packed-bed for increasing a cell density and achieving an efficient mass transfer, in which a cylindrical PUF block with many capillaries for medium flow was packed. Consequently, a high cell density of 1X10^7cells/cm^3-PUF was achieved and hepatocyte/spheroids were formed in the module. The urea synthesis rate of the module was 10 times higher than that of prototype module.3. A volume of the hybrid artificial liver module containing 1/10 amount of human liver hepatocytes was estimated to be about 2 liter by using the Multi-Capillary PUF packed-bed. This volume seemed to be a medically applicable value.4. We developed an extracorporeal circulation system for acute hepatic failure rat to investigate the performance of the artificial liver module in ex vivo experiment. The ammonia concentration in blood increased by actute failure was gone down to normal level by the artificial liver for 3 hour circulation and the hepatic failure rat was recovered.