Hepatocellular stem cells

Issue title: Stem Cells and Cancer

Guest editors: L. Mishra

Article type: Research Article

Authors: Kitisin, K.^a | Shetty, K.^{a; b; *} | Mishra, L.^c | Johnson, L.B.^{a; *}

Affiliations: [a] Department of Surgery, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA | [b] Department of Medicine, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA | [c] Department of Surgery, DVAMC, Washington, DC 20422, USA | Cancer Genetics, DVAMC and LCC, Georgetown University, Washington, DC, USA

Correspondence: [*] Corresponding authors: Lynt B. Johnson, MD, Chief of Liver Transplantation and Hepatobiliary Surgery, Georgetown University Hospital, 2 Main Building, 3900 Reservoir Rd., NW, Washington, DC 20007, USA. Tel.: +1 202 444 4557; Fax: +1 202 444 3701; E-mail: lynt.johnson@medstar.net. Kirti Shetty, MD, Medical Director, Liver Transplantation and Hepatobiliary Surgery, Georgetown University Hospital, 2 Main Building, 3900 Reservoir Rd., NW, Washington, DC 20007, USA. Tel.: +1 202 444 4557; Fax: +1 202 444 3701; E-mail: lynt.johnson@medstar.net.

Abstract: The liver has enormous regenerative capacity. Restitution of the liver in response to different injuries involves proliferation of cells at different levels of liver lineage. Mature hepatocytes, which are normally dormant, could undergo rapid replication with a near infinite capacity to proliferate. When the replication of mature hepatocytes is inhibited, a reserve compartment of bipotential hepatic progenitor/stem cells is activated. The degree of activation appears to correlate with the degree of inflammation and stage of chronic liver disease. Deregulation of key regulatory signaling pathways such as transforming growth factor-β, Wnt, hepatocyte growth factor, insulin-like growth factor, transforming growth factor-α and epidermal growth factor in this progenitor/stem cell population could give rise to HCC. Further understanding of these key signaling pathways and the molecular and genetic alterations associated with HCC could provide major advances in new therapeutic and diagnostic modalities.

Keywords: Hepatocellular progenitor/stem cells, oval cell, regeneration

DOI: 10.3233/CBM-2007-34-509

Journal: Cancer Biomarkers, vol. 3, no. 4-5, pp. 251-262, 2007