Administration of granulocyte colony-stimulating factor ameliorates radiation-induced hepatic fibrosis in mice

On the basis of the recent report that granulocyte colony-stimulating factor (G-CSF) treatment significantly improves survival and liver histology among chemically injured mice, we investigated whether G-CSF administration could contribute to faster recovery and promote tissue repair after local liver irradiation. Bone marrow chimeric female C57BL/6 mice were treated with G-CSF at days 7, 14, and 21 after local liver irradiation. We assessed the fibrosis index and the origin of proliferating cells reconstituting the liver at 2 or 5 weeks after radiation challenge. At day 35 after local irradiation, we observed G-CSF treatment to significantly reduce radiation-induced liver damage and collagen deposition. In addition, hepatic hydroxyproline levels and serum fibrosis markers in mice receiving G-CSF administration after radiation challenge were significantly lower compared with those of control mice. More importantly, histological examination suggested that recovery from hepatic damage was much better among the G-CSF-treated mice. Immunofluorescence and fluorescence in situ hybridization analyses revealed that donor cells engrafted into the host liver displayed epithelium-like morphology and expressed albumin, albeit at low frequency. These results suggested that G-CSF treatment initiated endogenous hepatic tissue regeneration in response to radiation injury and ameliorated its fibrogenic effects.