Hepatocyte growth factor promotes liver regeneration induced by transfusion of bone marrow mononuclear cells in a murine acute liver failure model.

Background/purpose: Bone marrow mononuclear cell (BMMC) transplantation has been shown to facilitate tissue and organ regeneration and repair. BMMC transplantation may be a potential therapy for acute liver failure, and its effect might be further improved. Hepatocyte growth factor (HGF) plays an important role in liver cell development, and may ameliorate hepatic fibrosis or cirrhosis in animal models. We therefore explored a potential synergistic effect of the co-application of HGF and BMMCs in liver regeneration following carbon tetrachloride (CCl(4))-induced acute hepatic injury.

Methods: We established a murine acute liver failure model induced by CCl(4) administration, and studied the effect of BMMC transplantation in combination with HGF. We used 4 groups of animals, one group was transfused with PKH26-labeled BMMCs (5 × 10(6)) and HGF [50 ng/(kg days) × 7 days] (BMMCs + HGF group), one group received BMMCs only, one group received HGF only, and one group received saline solution (0.9% NaCl) alone. The effects were examined by biochemical measurements of liver enzymes and quantitative image analysis for PKH26 labeling, and by determining proliferating cell nuclear antigen (PCNA) and albumin expression 4 weeks after the BMMC transplantation.

Results: PKH26-labeled BMMCs were detected in transplanted mouse livers, most of which expressed PCNA. PCNA and albumin expressions were increased significantly in the BMMCs + HGF group compared with the expressions of these parameters in the other 3 groups. Liver function, reflected by serum aminotransferase activity, was also improved in the BMMCs + HGF group relative to that in the other groups.

Conclusions: Data from the present study appear to suggest that BMMC transplantation combined with HGF administration exhibits a synergistic beneficial effect on improving both functional and histological liver recovery in a mouse model of acute liver failure.