Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: Identification of a human hepatic progenitor cell?
Article first published online: 30 DEC 2003
Copyright © 1999 American Association for the Study of Liver Diseases
Volume 30, Issue 1, pages 112–117, July 1999
How to Cite
Baumann, U., Crosby, H. A., Ramani, P., Kelly, D. A. and Strain, A. J. (1999), Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: Identification of a human hepatic progenitor cell?. Hepatology, 30: 112–117. doi: 10.1002/hep.510300140
- Issue published online: 30 DEC 2003
- Article first published online: 30 DEC 2003
- Manuscript Accepted: 27 APR 1999
- Manuscript Received: 11 DEC 1998
- Children's Liver Disease Foundation and from the Special Trustees of the United Birmingham Hospitals Endowment Fund. Grant Number: NL1721
The stem cell factor (SCF)/c-kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c-kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF). Specific expression of mRNA for c-kit and β-actin was measured by ribonuclease protection and by immunohistochemistry to localize c-kit in tissue sections. Expression of c-kit was detected at relatively consistent levels in normal and cirrhotic (EHBA) livers. However, in FHF, c-kit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence of small numbers of c-kit–positive cells in the portal tracts of normal livers with increased numbers in cirrhotic livers. The highest c-kit staining, however, was observed in FHF, in which, in addition to the cells in the portal tracts, discrete c-kit–positive cells were also found integrated into bile ducts. Colocalization studies demonstrated some of the c-kit–positive cells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-regulation of c-kit receptor expression in diseased livers suggests an involvement of this receptor/ligand system in hepatic repair mechanisms, and we speculate that c-kit–positive cells may represent a hepatic progenitor cell population. The origin and growth/differentiation potential of these c-kit–positive cells is under investigation.