The Effects And Mechanism Of Human Umbilical Cord Mesenchymal Stem Cells Modulating Apoptosis Cells In SLE

Background:Systemic lupus erythematosus(SLE)is an inflammatory autoimmune disease,involving in many organs dysfunctions.It is manifested by overactive T/B cells and accumulation of autoantibodies.The abnormality of apoptosis plays an important role in the pathogenesis of SLE.Umbilical cord(UC)-derived mesenchymal stem cells(MSCs)have been confirmed to exert therapeutic effects on SLE.However,whether the benefit effects of UC-MSCs on SLE were mediated by regulating apoptosis remains to be elucidated.Objective:We measured the T cells apoptosis in peripheral blood in SLE and performed the correlated analysis between the disease activity and the levels of clinic index,then explored whether UC-MSCs could exert the therapeutic action on SLE patients and lupus mice through regulating T cells apoptosis.Methods:Peripheral blood mononuclear cell(PBMC)was isolated from peripheral blood of SLE,SS,RA patients and HC.The late apoptosis rate of CD3+CD4+,CD3+CD8+ T cells was determined by FACS.The correlation analyses between the apoptosis of T cells and SLE Disease Activity Index(SLEDAI)or the level of clinic indexes,such as white blood cell(WBC),Platelet(PLT),complement 3,and complement 4 were further evaluated.PBMC or isolated CD4+,CD8+ T cells from SLE patients and healthy controls were cocultured with or without UC-MSCs(5:1)for 24 h.The apoptosis rate of CD4+ T and CD8+ T cells was detected by FACS.PBMC was isolated from peripheral blood of SLE patients before and 24 h after.MSCs transplantation,the apoptosis rate of CD3+CD4+ and CD3+CD8+ T cells was detected;B6.1pr mice were randomly divided into PBS and MSCs groups.1×106 UC-MSCs were injected into lupus mice via tail vein.B6.1pr mice injected with PBS and normal C57BL/6 mice were used as control groups.Six and 24 h later,all the mice were sacrificed,the apoptosis of lymphocyte in peripheral blood and spleen,the levels of immune cell subpopulation and cytokines in serum,the expression of Bim as well as Bcl-xl were detected.Results:The rate of T cells apoptosis was significantly higher in SLE patients compared to SS,RA and healthy controls.The apoptosis of T cells in SLE patients was positively correlated with SLEDAI score.The apoptosis of CD3+CD4+ T cells was negatively correlated with complement 3 and the number of PLT,while the apoptosis rate of CD3+CD8+ T cells was negatively correlated to the number of PLT and WBC.UC-MSCs could significantly inhibit the apoptosis rate of CD3+CD4+ and CD3+CD8+ T cells in PBMC of SLE and healthy controls.The apoptosis of isolated CD4+ T cells as well as CD8+ T cells in healthy control was downregulted by UC-MSCs in 24 h,while there was an inhibitory tendency in SLE patients.UC-MSCs suppressed the apoptosis of CD3+CD4+ T cells and CD3+CD8+ T cells in PBMC of SLE after transplantation for 24 h,while promoted the apoptosis of lymphocyte in B6.1pr mice.UC-MSCs transplantation could upregulate the percentage of Treg,while downregulate Thl,Th2 and plasma cells.UC-MSCs could reduce TGF-?1,but did not affect serum IFN-?,IL-1?,IL-6 levels and so on in lupus mice.UC-MSCs had little effects on the expression of Bim as well as Bcl-xl in T cells.Conclusion:UC-MSCs could inhibit T cell apoptosis of SLE patients,while increased the apoptosis of lymphocyte in B6.1pr mice,inhibiting UC-MSCs had a different effects on SLE patients and lupus mice.