Kinetic analyses of the performance of a hybrid-type artificial liver support system utilizing isolated hepatocytes

Abstract

In order to obrain sound criteria for the optimal design and improvement of the hybrid-type artificial liver support system (ALSS) utilizing isolated hepatocytes, theoretical and experimental evaluations of the performance of the ALSS were made based on the compartmental mass transfer model and reaction kinetics of cultured hepatocytes. Rate constants of the viability and metabolic reactions of the cultured hepatocytes were determined by batchwise suspension culture experiments, and the optimal conditions for hepatocyte culture were found to be in a relatively low range of dissolved oxygen tension in the culture medium. Results of in vitro and ex vivo perfusion experiments using a hollow-fiber type module or a rotating-disk type module indicated that experimentally obtained performances of the module in terms of hepatocyte viability and a few metabolic functions were well correlated with the theoretically estimated performances. Stimulation studies related to the design problems of a full-scale device revealed that the performance of the ALSS is inevitably limited by the viability of the hepatocyte. It was suggested that a considerable improvement in the performance of ALSS is to be attained by improving hepatocyte culture conditions.