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.