Experimental investigation of human bone marrow mesenchymal stem cells on acute-on-chronic liver failure in mice
Objective:To evaluate the therapeutic potential of human bone marrow mesenchymal stem cells(hBMSCs)on acute-on-chronic liver failure(ACLF)mice model.Methods:A total of 60 BALB/cJ mice were randomly divided into healthy control group(n=8)and ACLF model group(n=52).ACLF mice was established by intraperitoneal injection of carbon tetrachloride(CCl4).ACLF model group excluded dead mice were randomly divided into model group(n=11),hBMSCs low dose group(n=12),medium dose group(n=12)and high dose group(n=12).The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),total protein(TP),albumin(ALB)in mice were detect by a biochemical analyzer.Serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and chemokine ligand 1(KC/GRO)were detected by MSD elec trochemiluminescence technology.HE and Masson staining were used to evaluate the degree of pathological damage in liver tissue.Results:Compared with the control group,the serum level of TBIL,AST,ALT,TP and ALB were significantly increased(F=5.409,26.27,21.20,23.44,22.81,all P<0.001),AST/ALT was significantly decreased(F=3.036,P<0.05).Compared with the ACLF model group,the serum level of TBIL,AST and ALT were significantly decreased in the low,and medium dose group(all P<0.05),AST/ALT was significantly increased both in medium and high dose group(all P<0.05).The serum levels of pro-inflammatory cytokines IL-6 and KC/GRO were significantly decreased in low dose group(all P<0.05).IL-1β and TNF-α were significantly decreased in low,and medi-um dose group(all P<0.05),while anti-inflammatory cytokines IL-10 was significantly increased in the treated groups(all P<0.05).TP,ALB,IFN-γ,IL-2 and IL-5 were not significantly changed in all the treated groups(all P>0.05).The infiltration and necrosis area of inflammatory cells in the low and medium groups were significantly decreased(both P<0.05),and the positive area of collagen fibers in liver tissue was significantly reduced(both P<0.05).Conclusion:hBMSCs has an obvious therapeutic effect on CCl4-induced ACLF mice model and the therapeutic effect is not dose-dependent.In contrast,low-dose group has better therapeutic effect.
human bone marrow mesenchymal stem cellsacute-on-chronic liver failurecytokineshepatic fibrosis