Update on hepatic stem cells

The liver, like most organs in an adult healthy body, maintains a perfect b alance between cell gain and cell loss. Though normally proliferatively qui escent, simple hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes, a rapid regenera tive response to restore liver mass. This restoration of moderate cell loss and 'wear and tear' renewal is largely achieved by hepatocyte self-replica tion. Furthermore, cell transplant models have shown that hepatocytes can u ndergo significant clonal expansion. Such observations indicate that hepato cytes are the functional stem cells of the liver. More severe liver injury activates a facultative stem cell compartment located within the intrahepat ic biliary tree, giving rise to cords of biliary epithelia within the lobul es before these cells differentiate into hepatocytes. A third population of stem cells with hepatic potential resides in the bone marrow; these haemat opoietic stem cells can contribute to the albeit low renewal rate of hepato cytes, make a more significant contribution to regeneration, and even compl etely restore normal function in a murine model of hereditary tyrosinaemia. How these three stem cell populations integrate to achieve a homeostatic b alance is not understood. This review focuses on three aspects of liver ste m cell biology: 1) the hepatic stem cell candidates; 2) models of cell tran splantation into the liver; and 3) the therapeutic potential of hepatic ste m cells.