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

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1. Development of a hybrid artificial liver for clinical trialWe developed a hybrid artificial liver (HAL) which consists of a hepatocyte culture module with multi-capillary polyurethane foam packed-bed containing 200 g primary porcine hepatocytes and an extracorporeal circulation line. Almost all of the hepatocytes in the module formed spheroids, and they maintained the liver specific functions for at least 2 weeks. As preclinical study, the HAL was applied to about 25 kg warm ischemic liver failure pigs. In the preclinical study, we demonstrated its effectiveness such functions as suppression of increase of blood ammonia, maintenance of blood glucose, stabilization of vital sign and urinary excretion, extension of survival time. The HAL was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that the HAL has a strong possibility to be used in treating acute liver failure patients.2. Development of novel hybrid artificial liver module using hepatocyte organoid cultureAs a novel artificial liver module, we developed a hollow fiber module having a liver lobule-like structure, in which the hollow fibers representing blood vessels are arranged by spacers in a micro-regular arrangement within 150 μm. Inoculated hepatocytes in the extra-fiber space were formed in a lotus root-organoid by loading appropriate centrifugal force. The novel module achieved high cell density of about 4.0 x l0^7 cells / cm^3 - module and maintained better liver function compared to previous hollow fiber modules for several month. These results suggest that this novel module will be a new HAL for treatment of both chronic and acute liver failure patients, and for long-term bridge use for liver transplantation. Now we are investigating the optimization and scale up of the module.