Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Abstract

Liver failure, notwithstanding advances in medical management, remains a cause of considerable morbidity and mortality in the developed world. Although bioartificial liver (BAL) support systems offer the potential of significant therapeutic benefit for such patients, many issues relating to their use are still to be resolved. In this review, these issues are examined in terms of the functions required, the cells of choice in such a system, and the most appropriate environment to optimize the function of such cells T he development of nonbiological systems to support critically ill patients with acute liver failure (ALF) that incorporate plasmapheresis, 1 charcoal hemoperfusion, 2 and ultrafiltration techniques 3 has not had a significant impact on survival. Consequently, hepatocytebased biological systems have attracted intense interest worldwide but have also generated most of the controversy. Uncertainty exists about the most suitable biological component and the risk for zoonoses and immune rejection in the host. In addition, the optimization of culture conditions and thus metabolic function of the biological component have not been systematically studied, although continuing improvements in these areas have rendered this therapeutic avenue in ALF more promising. To compound matters, the question of which aspects of hepatocyte metabolism in an artificial liver are required to sustain life and promote recovery remains largely unanswered, further limiting development. In this review, the biological substrate of such systems is critically examined and insights are provided into the ideal system.

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Chlorzoxazone Metabolism by Porcine Cytochrome P450 Enzymes and the Effect of Cytochromeb5

“…Pigs are often explored as potential human models in pharmaceutical studies because of their wide availability and physiological, dietary, and anatomical similarity to humans (Balk, 1987;Monshouwer et al, 1998;Tsiaoussis et al, 2001). Drug development is a complex process requiring multiple steps before clinical trial testing.…”