Intermittent dosing of G-CSF to ameliorate carbon tetrachloride-induced liver fibrosis in mice.

On the basis of the recent report that granulocyte colony-stimulating factor (G-CSF) administration after rats' partial orthotopic liver transplantation greatly improved survival rate and liver regeneration of partial graft, we here evaluated the effect of intermittent administration of G-CSF on fibrosis formation induced by carbon tetrachloride (CCl(4)). Bone marrow chimeric female C57BL/6 mice were treated with G-CSF at days 1, 7, 14, 21, and 28 after CCl(4) challenge. At day 35 after CCl(4) administration, we found that G-CSF treatment significantly reduced CCl(4)-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice receiving G-CSF administration after CCl(4) challenge were significantly lower compared to those of control mice. Histological examination suggested that hepatic damage recovery was much better in these G-CSF-treated mice. Immunofluorescence and fluorescence in situ hybridization (FISH) analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology and expressed albumin, although at low frequency. These results suggest that intermittent G-CSF treatment might initiate endogenous hepatic tissue regeneration in response to CCl(4) injury and ameliorate its fibrogenic effects.