Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: Identification of a human hepatic progenitor cell?

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 pediatri c human liver during acute and chronic liver injury. Tissue was obtained fr om hepatectomy specimens of patients undergoing liver transplantation for e xtrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF), Spe cific expression of mRNA for c-hit and beta-actin was measured by ribonucle ase protection and by immunohistochemistry to localize c-kit in tissue sect ions. Expression of c-kit was detected at relatively consistent levels in n ormal and cirrhotic (EHBA) livers. However, in FHF, c-hit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence o f small numbers of c-hit-positive cells in the portal tracts of normal live rs with increased numbers in cirrhotic livers. The highest c-hit staining, however, was observed in FHF, in which, in addition to the cells in the por tal tracts, discrete c-hit-positive cells were also found integrated into b ile ducts. Colocalization studies demonstrated some of the c-kit-positive c ells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-r egulation of c-hit receptor expression in diseased livers suggests an invol vement of this receptor/ ligand system in hepatic repair mechanisms, and we speculate that c-hit-positive cells may represent a hepatic progenitor cel l population. The origin and growth/differentiation potential of these c-hi t-positive cells is under investigation.