Development of Hybrid Artificial Liver for Clinical Treatment of Fulminant Hepatic Failure Patient

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1. Establishment of mass isolation method of porcine hepatocytesWe established two step collagenase treatment method for mass isolation of porcine hepatocytes. This method consists of liver perfusion and cell process using collagenase solution. More than 380g porcine hepatocytes (viability : more than 85%) were isolated within 3 hours from two pig livers (570g) by this method.2. Development of a hybrid artificial liver for children treatmentWe developed a multi-capillary polyurethane foam (PUF) packed-bed module (diameter : 7.7cm, height : 20cm, volume : 1000cmィイD13ィエD1) with 100g of porcine hepatocytes for clinical application. Porcine hepatocytes in the module formed spheroids within 24 hours of culture and maintained liver specific functions at least 10days of culture. We also developed extracorporeal circulation system for an artificial liver treatment, with control of DO, pH and temperature in plasma, and refinement of circulation loop for sufficient mass transfer.3. Preclinical tests of a hybrid artificial liver using failure pigsAs a preclinical test, we developed as artificial liver module with 200g of porcine hepatocytes, and applied to warm ischemic liver failure pigs of 25kg. Consequently, we could successfully indicate the care effect by the artificial liver in suppression of increase of blood ammonia, maintenance of blood glucose, extension of survival time and so on.4. Study of modulation of immunologic reaction between human serum and porcine hepatocytesWhen the porcine hepatocytes were cultured in human serum, immunologic reaction of human C3 against porcine hepatocytes occurred positively. We found that damage of porcine hepatocytes by human C3 could be decreased by the addition of nafamostat mesliate.These results suggest that our device will become a promising method for clinical treatment. At present, the device have been applied to the Ethics Committee of Kyushu University for clinical application.