Development of a Hybrid Artificial Liver for Treatment of Chronic Liver Failure Patients

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1.Evaluation of hybrid artificial liver module by applying liver failure rat.We developed a novel module, which applied our original hepatocytea orgahoid culture technique using centrifugal force. The module consists of many hollow fibers arranged regularly at submillimeter order, which imitated the structure of liver lobule. And we accomplished scale-up of this module from 1.8cm^3 that uses 0.6g hepatocytes to 9.0cm^3 that uses 3.0g hepatocytes.We developed an extracorporeal circulation system that allows blood to flow directly from the animal through the artificial liver module and then to return to the animal. Our original artificial liver module with 3.0g primary rat hepatocytes was applied to a liver failure rat by using this system. At the result, the artificial liver module was effective for recovery or elongation of survival time of liver failure rat.2.Development of organoid sheet cultureWe developed a novel method to form an organoid having sheet-like shape to be able to control thickness of organoid and to suppress the generation of necrotic cell layer inside the organoid. Hepatocyte organoid sheet could express liver specific functions about 1.5 times higher than that of hepatocyte cylindrical organoid, which formed inside hollow fiber. This culture technique may be useful for development of a novel hybrid artificial liver, or a patch for graft of injured tissue.