Effects Of Bone Marrow Mesenchymal Stem Cells-derived Soluble Components On Expression Of Vescular Endothelial Growth Factor And Liver Regeneration In Rats

Objectives:To investigate the effects of soluble components derived from bone marrow mesenchymal stem cells on the expression of vescular endothelial growth factor (VEGF) and liver regeneration induced by70%portal branch ligation (PBL) in rats.Materials and methods:Isolated and cultured BMSCs were lysed by sonication. PBL was performed in male SD rats followed by splenic injection of BMSCs or PBS as control. Animals were analyzed for liver regeneration index, proliferation of both hepatocytes and sinusoidal endothelial cells (SECs), hepatic function, histopathologic change and hepatic genes expression. Expression of VEGF were also assessed by Western blot and immunohistochemistry.Results:The liver regeneration index increased in BMSCs group especially48h and120h after PBL compared with the control group (P<0.05) and reached (51.71±1.62)%、(76.82±0.81)%, respectively. A2-fold increase was showed in the PCNA labeling index of hepatocytes and SECs in animals treated with BMSCs. Histopathological findings showed that vacuolar change and sinusoidal congestion were lower in BMSCs group. Microvessel density (MVD) was higher in BMSCs group. Alanine transaminase(ALT) and Aspartate transferase (AST) showed no significant difference between two groups (P>0.05). On48h post operation, hepatic interleukin-6(IL6),tumor necrosic factor a(TNFa),hepatocyte growth factor(HGF) vescular endothelial growth factor A(VEGFA) and vescular endothelial growth factor receptor2、 3(VEGFR2、VEGFR3) mRNAs tended to increase in BMSCs group (P<0.05) while transform growth factor β1(TGFβ1) mRNA decreased (P<0.05). Notably, compared to the control group, the high level expression of VEGFA and VEGF2、3mRNA remained until120h after surgery(P <0.05). Western blot showed that the expression level of VEGF in two groups were equal on both48h and120h afer surgery (P>0.05).On48h post operation, positive VEGF immunoreactivity was present in both periportal and pericentral hepatocytes in BMSCs group,while only in periportal hepatocyte in the control group.Conclusion:These results demonstrated that BMSCs accelerate liver regeneration caused by PBL, which may result from hepatoprotective, enhanced hepatocyte as well as SECs proliferation and angiogensis early after operation, potentially creating a new avenue for the study of hepatic regeneration.