The impact of human umbilical cord mesenchymal stem cells on the Wnt/β-catenin signal expression in rats with acute liver failure

Abstract

Objective To study the therapeutic effects of human umbilical cord mesenchymal stem cells (hUCMSC) on acute liver failure (ALF) in rats and the impact on expression of Wnt/β-catenin signal. And to explore the possible mechanisms of hUCMSC in activating liver regeneration in rats with ALF. Methods One hundred of the 105 rats were intraperitoneal injected with D-galactosamine to build ALF model and the remaining 5 rats were intraperitoneal injected with 0.9% NaCl solution. The ALF rats were divided into two groups with 50 in each group, which received either hUCMSC (hUCMSC group) or 0.9% NaCl solution (control group) through tail-intravenous injection. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured and compared between groups. Liver histology changes and survival rates were also compared between two groups. The relative expressions of Wnt/β-catenin signal related genes including Wnt2, Wnt7a and Wnt7b were determined by quantitative real-time polymerase chain reaction analysis. The expressions of β-catenin in both groups were evaluated by immunohistochemistry (IHC) and immunofluorescence (IF) analysis. Student t test and Wilcoxon test were used for statistical analyses. Results One day after tail-intravenous injection, the levels of ALT ([906.0±76.9] U/L vs [1 874.7±191.3] U/L; t=4.697, P=0.009) and AST ([1 138.0±221.5] U/L vs [2 239.7±213.3] U/L; t=3.583, P=0.023) in hUCMSC group and control group were statistically different. Death rate within 7 d of hUCMSC group was significantly lower than that of control group (10% vs 50%, χ2=4.048, P=0.044) and the liver damage was alleviated in hUCMSC group. IHC and IF analysis revealed that β-catenin mainly accumulated in the cytoplasm and nuclear and was more abundant in hUCMSC group. The expressions of Wnt2, Wnt7a and Wnt7b of hUCMSC group were 2.4 folds (t=3.950, P=0.017), 3.1 folds (t=4.846, P=0.008) and 3.0 folds (t=2.888, P=0.045), respectively, which were all higher than those of control group. Conclusions Transplanting hUCMSC into ALF rats could improve the liver function, alleviate liver damage, stimulate the liver regeneration and decrease death rate. The activation of Wnt/β-catenin signal may be involved in this process, which leads to the liver regeneration. Key words: Liver failure, acute; Human umbilical cord mesenchymal stem cells; Wnt/β-catenin