Mesenchymal Stem Cells Alleviate Acute Liver Failure through Regulating Hepatocyte Apoptosis and Macrophage Polarization  

作　　者：Yachao Tao Yonghong Wang Menglan Wang Hong Tang Enqiang Chen 

机构地区：[1]Center of Infectious Diseases,West China Hospital,Sichuan University,Chengdu,Sichuan,China [2]Division of Infectious Diseases,State Key Laboratory of Biotherapy,Sichuan University,Chengdu,Sichuan,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第6期571-580,共10页临床与转化肝病杂志（英文版）

基　　金：supported by the National Key Research and Development Program of China(2022YFC2304800);the Science and Technological Supports Project of Sichuan Province in China(2022YFS0094).

摘　　要：Background and Aims:Acute liver failure(ALF)is a life-threatening clinical problem with limited treatment options.Administration of human umbilical cord mesenchymal stem cells(hUC-MSCs)may be a promising approach for ALF.This study aimed to explore the role of hUC-MSCs in the treat-ment of ALF and the underlying mechanisms.Methods:A mouse model of ALF was induced by lipopolysaccharide and d-galactosamine administration.The therapeutic effects of hUC-MSCs were evaluated by assessing serum enzyme activity,histological appearance,and cell apoptosis in liver tissues.The apoptosis rate was analyzed in AML12 cells.The levels of inflammatory cytokines and the phenotype of RAW264.7 cells co-cultured with hUC-MSCs were detected.The C-Jun N-terminal kinase/nuclear factor-kappa B signal-ing pathway was studied.Results:The hUC-MSCstreatment decreased the levels of serum alanine aminotransferase and aspartate aminotransferase,reduced pathological damage,alleviated hepatocyte apoptosis,and reduced mortality in vivo.The hUC-MSCs co-culture reduced the apoptosis rate of AML12 cells in vitro.Moreover,lipopolysaccharide-stimulated RAW264.7 cells had higher levels of tumor necrosis factor-α,interleukin-6,and interleukin-1β and showed more CD86-positive cells,whereas the hUC-MSCs co-culture reduced the levels of the three inflammatory cytokines and increased the ratio of CD206-positive cells.The hUC-MSCs treatment inhibited the activation of phosphorylated(p)-C-Jun N-terminal kinase and p-nuclear factor-kappa B not only in liver tissues but also in AML12and RAW264.7 cells co-cultured with hUC-MSCs.Conclusions:hUC-MSCs could alleviate ALF by regulating hepatocyte apoptosis and macrophage polarization,thus hUC-MSC-based cell therapy may be an alternative option for patients with ALF.

关 键 词：Human umbilical cord mesenchymal stem cells Acute liver failure Hepatocyte apoptosis HEPATITIS Macrophage polarization LPS/D-GalN 

分 类 号：R575.3[医药卫生—消化系统]