Bone marrow stem cells and liver disease

Liver cell mass can be restored via an average of less than two cell division cycles, albeit individual hepatocytes seem to have an intrinsic capacity for up to 70 doublings in serial transplantation experiments. 1 At times of overwhelming cell loss, with longstanding iterative injury (eg, chronic viral hepatitis), or when hepatocyte replication is impeded (eg, replicative senescence of steatohepatitis), regeneration seems to occur via a second cell compartment. 2, 3 This compartment remains poorly defined and seems to arise from a less differentiated cell population within the terminal branches of the intralobular biliary tree- the canals of Hering. 4 In rodents these cells are called oval cells, but in humans they are more aptly named hepatic progenitor cells. 5 Attempts to identify the originating stem cell are hampered by a paucity of specific cell surface markers. Using Y chromosome tracking, a sparse number of hepatocytes seemed to be originating from the BM in male recipients of female orthotopic liver transplants, and in females who had received bone marrow transplantation (BMT) from male donors and thereafter developed liver disease. 6, 7 Similarly, other epithelial tissues, such as gut and skin, seemed to harbour cells of BM origin. 8 Investigators then turned to an animal model of hereditary type I tryosinaemia, the fumarylacetoacetate hydrolase knockout mouse (FAH(-/-)), in which it seemed that this potentially fatal enzyme deficiency could be rescued through repopulation of the abnormal liver by BM cells derived from wild-type donors.