Development of an hybrid artificial liver for human medical use equipped with the newest regulation system for control of culture environment of hepatocytes

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1. We developed a prototype module (multi-capillary PUF packed-bed) of hybrid artificial liver for recovery of hepatic failure dogs, which was required for an evaluation of the performance of this module using PUF/spheroid packed-bed for human medical use. Last year, we could succeed in recovery of a hepatic failure rat treated by 5cm^3 of module containing about 5*10^7 cells which corresponded to about 10% of liver cells. In the case of dog, we designed about 300cm^3 of module containing 3*10^9 cells (30g of cells) which corresponded to about 10% of dog liver cells. The diameter and the pitch of a capillary were 2mm and 4mm, respectively.2. Opimum flow rate of medium/plasma related to reveal the maximum performance of the hybrid artificial liver module was calculated to be 400 ml/min from the results of small scale experiment using rat. Dissolved oxygen concentration (DO) gradient occurred in the module seemed to be avoided by bi-directional flow of medium inside of the module. The performance which indicated by albumin secretion rate of hepatocytes immobilized in the module under pH ; 7.2 and DO ; 6.5 of controlled culture condition, was comparable with static culture of hepatocytes. These results indicated that the scale up of module was successful.3. We applied this artificial liver module to acute ischemic liver failure dogs for evaluation of practicality of the module for human medical care, and investigated the change of some biochemical components in blood as index of liver function. Consequently, we could succeed in the maintenance blood glucose level and ketone body ratio, and suppress the increase of blood ammonia and bilirubin levels. These results suggest that the artificial liver module is a promising equipment for recovery of hepatic failure condition in medical use.