Adipose-derived Mesenchymal Stem Cells Protect Against Liver Transplantation Reject And Its Possible Mechanism

Objective:Recent research indicates that adipose-derived mesenchymal stem cells (ADMSCs) may relieve the rejection effect after liver transplantation. This study was designed to make a research on the after-immunological rejection effect and possible mechanism for inhibition of ADMSC on rat liver transplantation.Methods:SD rats were taken for isolated culture of ADMSCs and identification of its immunologic phenotype. RNA interference lentiviral vector was established for transfection of ADMSCs, interruption of PD-L1, and comparison of PD-L1expression difference. Two-cuff technique was used to establish rat donor-acceptor orthotopic liver transplantation acute rejection models, which were divided into Group A-SD-Wistar orthotopic liver transplantation andinfusion of physiological saline, Group B and C-SD-Wistar orthotopic liver transplantation and infusion of ADMSCs with different schemes, and Group D-SD-Wistar orthotopic liver transplantation and infusion of lentiviral transfected ADMSCSs. Comparison was made for the differences in liver function, IL-2and IL-10of three groups of rats after liver transplantation, the liver pathology changes and stem cell apoptosis and the difference in expressions of Bcl-2and Bax of liver tissues.Results:The results turned to successfully acquire ADMSCs via isolated culture, and the expression of PD-L1mRNA in ADMSCSs after lentiviral transfection decreased significantly. The differences for theose groups of rats liver transplantation models in ALT, AST and TBIL turned to be of statistic significance (P<0.05), and the ADMSCs treated ALT, AST and TBIL levels of Group B and C were significantly lower than those of Group A and D (P<0.05) while ALT, AST and TBIL levels of Group D were significantly lower than those of Group A (P<0.05). Serum IL-2level of Group B and C rat liver transplantation model was significantly lower than that of Group A and D (P<0.05), while Serum IL-10level of Group B and C was greatly higher than that of Group A and D (P<0.05); Serum IL-2level of Group D rat liver transplantation model was lower than that of Group A (P<0.05), while Serum IL-10level of Group D was greatly higher than that of Group A (P<0.05). TUNEL was used to detect liver cell apoptosis, the number of apoptotic cells in liver tissue slice of such three groups of rats was, successively, A>C>B and C. Apoptotic indexes of Group A, B,C and D were35.86±5.92,12.39±2.23,13.76±4.23and28.47±4.32, respectively, which was of statistic significance (for all, P<0.05). After conducting liver transplantation model operation for Group B and C rat, the expression of Bcl-2was found to be greatly higher than that of Group A and D, while the expression of Bcl-2of Group D turned to be higher than that of Group A. The expression of Bax for Group B and C rats after liver transplantation model operation showed a value significantly lower than that of Group A and Group D, however, the expression for Group D was significantly lower than that of Group C.Conclusions:The adipose-derived mesenchymal stem cells can significantly reduce after liver transplantation rejection, but the best injection timing and dose remain to be further studied.PD-L1pathway may play an important role in its inhibition of rejection.