Hepatic stem cells: A review

The existence of a liver stem cell population has only gained credence rece ntly, following the results of animal experiments. These cells are thought to reside in the terminal bile ductules (canals of Hering). Hepatocyte divi sion is responsible for liver regeneration after most causes of injury. How ever, stem cells may contribute to hepatocyte regeneration, or even take ov er this role if the liver injury is severe and associated with an impairmen t of hepatocyte proliferation as in cirrhosis or submassive/massive necrosi s, due to drugs, toxins or viruses. "Oval" cells are the descendants of the stem cells and are found in the portal and periportal regions in experimen tal animals within days of the liver injury. These cells proliferate to for m narrow ductules, which may stain positively for biliary cytokeratins CK 1 9, and radiate out into the damaged parenchyma. Both in vitro and in vivo a nimal studies now suggest that oval cells can differentiate into bile ductu lar cells or hepatocytes to allow repopulation of the injured liver. As the oval cells differentiate into hepatocytes they may show positive staining for pyruvate kinase isoenzyme L-PK, albumin and alpha-fetoprotein. There is also growing evidence that bone marrow stem cells may contribute to liver regeneration. The possible involvement of hepatic stem cells in the develop ment of dysplastic nodules, hepatocellular carcinoma and cholangiocarcinoma has been suggested but remains highly controversial. Oval cell isolation a nd culture techniques, together with stem cell transplantation strategies, may in the future provide novel treatments for individuals with inherited a nd acquired hepatic disorders.