[Effect of basic fibroblast growth factor treatment on efficacy of adipose-derived mesenchymal stem cells in liver cirrhosis]

Abstract

Objective: To observe the effect of basic fibroblast growth factor (bFGF) treatment on efficacy of adipose-derived mesenchymal stem cells (ADSCs) in cirrhotic rats. Methods: A rat model of liver cirrhosis was established via intraperitoneal injection of carbon tetrachloride (CCl(4)) for 10 weeks. Thirty SD rats were randomly divided into 3 groups (n = 10): control group served as group A, and 0.5ml of phosphate-buffered saline (PBS) was transfused into the tail vein; ADSCs single-dose transplantation group served as group B, and 1×10(6) ADSCs were transplanted into the tail vein; bFGF-treated ADSCs treatment group served as group C, and 1×10(6) bFGF-treated ADSCs were transplanted through tail vein. Liver function, pathological and cytokine changes, and the in vivo survival transformation condition of the transplanted cells were measured at one week after transplantation. F test and an independent sample t test were used. Results: bFGF treatment had significantly promoted the proliferation, differentiation and overexpression of hepatocyte growth factor (HGF) in ADSCs [ADSCs single: (2 137.16 ± 261.52) pg/ml vs. ADSCs (bFGF): (4 776.23 ± 532.44) pg/ml, P < 0.05]. The bFGF-treated ADSCs treatment group had statistically significant differences in promoting the recovery of liver function [alanine aminotransferase (ALT): ADSCs single (190.8 ± 34.98) vs. ADSCs (bFGF): (117.8 ± 35.81) pg/ml; aspartate aminotransferase (AST): ADSCs single (295.2 ± 33.71) U/L vs. ADSCs (bFGF): (183.8 ± 41.29) U/L, P ​​< 0.05). There was no statistically significant difference in serum albumin levels between the control group, ADSCs single group, and ADSCs (bFGF) group. Compared with the control group, the serum albumin level of ADSCs (bFGF) group was increased significantly (P < 0.05), and the difference between the control group and the ADSCs single transplantation group in improving liver regeneration and reducing liver damage was statistically significant (P < 0.05). Masson trichrome staining showed that the percentage of the liver fibrosis area in the bFGF-treated ADSCs treatment group was 6.78% ± 0.56%, which was significantly higher than that of the control and ADSCs single dose transplantation group (7.96% ± 0.64%) (P < 0.05). Western blot analysis showed that the expression of HGF protein in the bFGF-treated ADSCs treatment group was significantly up-regulated, while the expression of α-smooth muscle actin was significantly down-regulated, and the difference was significant in the ADSCs single transplantation group. A double fluorescent staining method showed that the numbers of stem cells implanted in the liver tissue of the bFGF-treated ADSCs treatment group were higher than that of the ADSCs single transplantation group. In-vitro cell experiments confirmed that bFGF had significantly promoted the overexpression of HGF in ADSCs. Conclusion: bFGF-treated ADSCs transplantation can significantly improve liver function and fibrosis as compared with ADSCs single-dose transplantation in cirrhotic rats.

Keywords: Adipose tissue derived mesenchymal stem cells; Basic fibroblast growth factor; Hepatocyte growth factor; Liver cirrhosis.