Xenogenetic Bioartificial Liver

The liver is a major plant in human body. It performs many synthetic functions, such as producing albumin and clotting factors, balances the chemical environment including glucose and amino acid concentrations, and metabolizes or detoxifies many drugs and waste products of the body？HH？HHs metabolism. Because of the liver's structural complexity and functional diversity, our quest for finding an artificial replacement or semisynthetic surrogate has been initiated. Over 4,500 people die of liver failure every year in Taiwan. Mortality rates are particularly high for those diagnosed with acute fulminant hepatic failure (FHF) because hepatic regeneration is neither rapid nor sufficient enough to sustain the patient. The only cure for many liver failure patients is liver transplant or spontaneous regeneration by the liver itself. Because of the shortage of donor organs, many patients cannot receive a transplant. Many patients in hepatic failure do not qualify for transplantation because of concurrent medical problems, such as active alcoholism, or concomitant infection. Those who do qualify for a liver transplant often die while awaiting an allograft because of the scarcity of donor organs. Due to the critical need, there have been necessary to develop bioartificial liver system in Taiwan where concern for liver disease is more serious than western countries. Here, we propose research proposals to solve basic problems associated with this xenogeneic liver assist devices prior to its clinical application. Our specific aims of this project are as follows. 1. To establish the methodology for large scale isolation and culture of rabbit hepatocyte, and examine the kinetics and characterization of spheroid formation 2. To design and establish animal (pig) models of fulminant hepatic failure and characterize the biochemical and neurological status of animal 3. To integrate BAL device established from rabbit hepatocyte spheroids into different prototypes of hollow fiber membrane and test for their functional performance 4. To design an on-line monitoring system for optimizing the performance of BAL 5. To evaluate the efficacy of the BAL on improving the survival of pigs with liver failure and characterize the biochemical and neurological status of pigs during BAL treatment To follow up the immunological responses of the survived animals

Project ID:PG9205-0298
External Project ID:NHRI-EX92-9009EL