Development of high performance hybrid artificial liver and its evaluation in preclinical test

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1.We developed a perfusion culture system of porcine hepatocyte spheroids (module volume ; 18.8cm^3, cell weight ; 2g, total plasma volume ; 140ml), and evaluated the functions of the spheroids in plasma of hepatic failure patient. Porcine hepatocyte spheroids mainatained ammonia decreasing activity in human plasma at least 3 days of culture.2.For a validation of the performance of our artificial liver using large animals, we made hybrid artificial liver module (multi-capillary polyurethane foam (PUF) packed-bed, vulume ; 380 cm ^3) containing 30 g of dog hepatocyte which corresponded about 10% of a dog liver weight. When the module was applied to ischemic liver failure dogs (body weight ; 15 kg), blood glucose concentration was maintained, increase of blood ammonia concentration was suppressed and so on by the artificial liver treatment. These performances were comparable or slightly superior than those of Demetriou's artificial liver which was already used clinically as a bridge use for liver transplantation.3.As preclinical step, we developed an artificial liver module using porcine hepatocyte spheroids (volume ; 380 cm^3*2) containing 64 g of cells, and applied to ischemic liver failure pigs (body weight ; 25 kg). Consequently, we could succeed suppression of the increase of blood ammonia concentration and extension of survival time.These results suggest that our hybrid artificial liver system is a promising equipment for recovery from hepatic failure condition in human medical care.