Serum IFN‐γ Predicts the Therapeutic Effect of Mesenchymal Stem Cells Transplantation in Systemic Lupus Erythematosus Patients
نویسندگان
چکیده
Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) show immunoregulatory properties on various immune cells and display therapeutic effects on various autoimmune diseases such as systemic lupus erythematosus (SLE). The aim of this study was to investigate the effect of the SLE environment on UC MSCs and to identify a potential serum biomarker to predict the therapeutic effect. UC MSCs were cocultured with peripheral blood mononuclear cells (PBMCs) from active lupus patients, and the proliferation, apoptosis and surface markers of UC MSCs were observed. UC MSC functional molecules were assessed by real-time polymerase chain reaction, and the signaling pathways were analyzed by Western blot. The clinical effect of MSC transplantation (MSCT) for lupus patients was followed-up, whereas baseline serum cytokines were analyzed by enzyme-linked immunosorbent assay. The coculture of PBMC from lupus patients promoted MSC proliferation. Lupus PBMCs were more potent in stimulating UC MSCs to secrete vascular endothelial growth factor (VEGF) and CXCL-12. Furthermore, lupus PBMCs activated Akt, IκB, and Stat5 signaling pathways in UC MSCs but did not affect Erk1/2 and Smad1/5/8 pathways. Moreover, our clinical study showed that higher baseline levels of IFN-γ might predict a good response to MSCT in active lupus patients. Baseline IFN-γ levels may predict clinical response to MSC therapy for active lupus patients, which will help to choose suitable patients for clinical transplantation. Stem Cells Translational Medicine 2017;6:1777-1785.
منابع مشابه
IL-17 is Aberrantly Overexpressed Among Under-treatment Systemic Lupus Erythematosus Patients
Background & Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic inflammatory immune response. Current therapies mostly rely on glucocorticoids which are accompanied by side-effects and mostly fail to achieve a favorable remission. Th17 subpopulation of T cells is increased in exacerbated SLE as IL-17 cytokine is overexpressed. ...
متن کاملEffects of 1,25-dihydroxyvitamin D3 on IL-17/IL-23 axis, IFN-γ and IL-4 expression in systemic lupus erythematosus induced mice model
Objective(s): Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of...
متن کاملTherapeutic effects of umbilical cord blood-derived mesenchymal stem cell transplantation in experimental lupus nephritis.
Mesenchymal stem cells (MSCs) have been shown to possess immunomodulatory properties. Systemic lupus erythematosus is an autoimmune disease that results in nephritis and subsequent destruction of renal microstructure. We investigated whether transplantation of human umbilical cord blood-derived MSCs (uMSCs) is useful in alleviating lupus nephritis in a murine model. It was found that uMSCs tran...
متن کاملDouble Allogenic Mesenchymal Stem Cells Transplantations Could Not Enhance Therapeutic Effect Compared with Single Transplantation in Systemic Lupus Erythematosus
The clinical trial of allogenic mesenchymal stem cells (MSCs) transplantation for refractory SLE patients has shown significant safety and efficacy profiles. However, the optimum frequency of the MSCs transplantation (MSCT) is unknown. This study was undertaken to observe whether double transplantations of MSCs is superior to single transplantation. Fifty-eight refractory SLE patients were enro...
متن کاملA CD8 T Cell/Indoleamine 2,3-Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus
OBJECTIVE Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. METHODS The effects of allogeneic umbilical cord-derived MSCs (UC-MSCs) on inhibiti...
متن کامل