Effect of mesenchymal stem cells combined with immunosuppressants on immune rejection in a rat model of liver transplantation / 临床肝胆病杂志

ABSTRACT

ObjectiveTo investigate the effect of mesenchymal stem cells （MSCs） combined with immunosuppressants （IS） on immune rejection in a rat model of liver transplantation. MethodsF344 rats were divided into Normal group （without any intervention）， PS group （injected with an equal volume of normal saline）， MSC group （injected with MSC）， IS group （injected with IS）， and MSC+IS group （injected with MSC and IS）， with 8 rats in each group. For all rats except those in the Normal group， the Kamada’s double-cuff method was used to establish a model of orthotopic liver transplantation， without reconstruction of the hepatic artery. HE staining and Masson staining were performed for rat liver tissue， and the degree of liver fibrosis was analyzed； immunohistochemical experiments were used to measure the infiltration of T cells and NK cells， and immunofluorescence assay was used to analyze macrophage M2 polarization. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kaplan-Meier method was used to plot survival curves， and the log-rank test was used for survival analysis. ResultsCompared with the PS group， the MSC+IS group had a significantly prolonged survival time （P<0.01）， and the MSC group， the IS group， and the MSC+IS group had a significant improvement in the histological structure of the liver and a significant reduction in the degree of liver fibrosis （all P<0.000 1）， as well as a significant reduction in the infiltration of NK and T cells （all P<0.000 1） and a significant increase in the degree of macrophage M2 polarization （all P<0.000 1）. The MSC+IS group had a significantly better effect than the MSC group and the IS group. ConclusionMSCs combined with IS can improve liver histopathology， reduce inflammatory cell infiltration， promote macrophage M2 polarization， and exert an immunosuppressive effect in rats after liver transplantation.