Mechanism of bone marrow mesenchymal stem cells in hepatic ischemia-reperfusion injury in mice
Objective This study aims to investigate the effects of bone marrow mesenchymal stem cells(BMSCs)on lymphocyte subsets and cytokine expressions in mice with hepatic ischemia-reperfusion injury(HIRI).Methods A total of 18 mice with 6-8 weeks old were randomly divided into sham operation group(sham group),HIRI group,and BMSCs intervention group(BMSC group),with 6 mice in each group.Changes in liver function and pathology,as well as the apoptosis of liver cells were evaluated in each group.Additionally,the levels of CD4+T cells,natural killer(NK)cells in peripheral blood,and nine cytokines(interleukin-2[IL-2],IL-4,IL-5,IL-6,IL-10,IL-12,IL-17,tumour necrosis factor alpha[TNF-α],and interferon-gamma[IFN-γ])in serum were measured for each group.Results Mice in the sham group had a normal liver structure,while those in HIRI group had severely damaged liver structure.Mice in BMSC group had a milder damage in the liver.The histological score for liver tissue damage was significantly lower in the BMSC group compared to the HIRI group(P<0.05).The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in peripheral blood increased in the HIRI group compared to those of the sham group(P<0.05),but they were comparable between BMSC group and HIRI group.The number of apoptotic cells in liver tissues was significantly higher in the HIRI group compared to that of the BMSC group and the sham group(P<0.05).Moreover,the levels of CD4+T cells and NK cells in peripheral blood were significantly lower in the BMSC group compared to those of the HIRI group(P<0.05).However,the levels of IL-2,IL-6,and IL-10 showed no significant differences between HIRI group and BMSC group.Among the nine cytokines detected,serum levels of IL-4,IL-5,IL-12 and IL-17 significantly increased,while the levels of TNF-α and IFN-γdecreased in the BMSC group compared to those of the HIRI group(P<0.05).Conclusion Transplantation of BMSCs in the process of repairing hepatic ischemia-reperfusion injury improves liver function,reduces cell apoptosis,and regulates cytokine release by inhibiting the expressions of lymphocyte subsets(CD4+T cells and NK cells),decreasing pro-inflammatory factors,increasing anti-inflammatory factors,and maintaining cytokine homeostasis in the HIRI environment.
bone marrow mesenchymal stem cellsliver functionpathology alterationhepatic ischemia-reperfusion injury