A Hepatocyte Spheroids-Based Bioartificial Liver System

抄録

Bioartificial liver (BAL) is an extracorporeal liver support system, which contains biological components such as hepatocytes as a biocatalyst. The BAL will act as a bridge to provide patients with the extension of survival time until a donor organ becomes available for transplantation or their own liver can be regenerated. The performance of a BAL depends on the functional activities of the hepatocytes immobilized in the system. However allogenic hepatocytes from human livers are poorly available, so xenogenic hepatocytes, usually porcine hepatocytes have been used in BAL. The cells are immobilized as a form of single cells or spheroids inside the beads. But the efficient culture technology to form a lot of hepatocytes, 1x1010 cells into spheroids in large scale is not yet developed. The reasons are oxygen limitation and shear stress in large volume of suspension vessel. We achieved a high viability and functionality of porcine hepatocyte spheroids through application of simple modification of media without any addition of apparatus. As in vitro and in vivo results, we could recover enough spheroids and these cells showed high ammonia removal capacity in preclinical treatment of anhepatic pig.