Biologic liver support: Optimal cell source and mass

Hepatic support is indicated in acute liver failure (ALF) patients to foster liver regeneration, or until a liver becomes available for orthotropic liver transplantation (OLT), in primary non function of the transplanted liver, and hopefully in chronic liver disease patients affected by ALF episodes, in whom OLT is not a therapeutic option. The concept of bioartificial liver (BAL) is based on the assumption that only the hepatocytes can perform the whole spectrum of biotransformation functions, which are needed to prevent hepatic encephalopathy, coma and cerebral edema. Among others, two important issues are related to BAL development: 1) the choice of the cellular component; 2) the cell mass needed to perform an adequate BAL treatment. Primary hepatocytes, of human or animal origin, should be considered the first choice because they express highly differentiated functions. Accordingly, a minimal cell mass corresponding to 10% of a human adult liver, i.e. 150 grams of freshly isolated, greater than or equal to90% viable hepatocytes should be used. When 4 degreesC cold-stored or cryopreserved hepatopytes are used, the cellular mass should be increased because of a drop in cell viability and function. In case of hepatoma-derived cells, cultured cell lines or engineered cells, an adequate functional cell mass should be used, expressing metabolic and biotransformation activities comparable to those of primary hepatopytes. Finally, the use of porcine hepatocytes or other animal cells in BAL devices should be presently directed only to ALF patients as a bridge treatment to OLT because of potential transmission of animal retrovirus and prions which may potentially cause major pandemics.