Serum IFN-γ Predicts the Therapeutic Effect of Mesenchymal Stem Cells Transplantation in Systemic Lupus Erythematosus Patients.

Serum IFN-γ Predicts the Therapeutic Effect of Mesenchymal Stem Cells Transplantation in Systemic Lupus Erythematosus Patients.
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血清 IFN-γ 预测系统性红斑狼疮患者间充质干细胞移植的治疗效果

DOI:
10.1002/sctm.17-0002
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发表时间:
2017-09
影响因子:
6
通讯作者:
Sun L
Sun L
中科院分区:
医学2区
文献类型:
--
作者:
Wang D;Wang S;Huang S;Zhang Z;Yuan X;Feng X;Lu L;Sun L

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脐带(UC)来源的间充质干细胞(MSC)对各种免疫细胞具有免疫调节特性,并对各种自身免疫性疾病(如系统性红斑狼疮(SLE))具有治疗作用。本研究的目的是研究SLE环境对UC MSC的影响,并确定一个潜在的血清生物标志物来预测治疗效果。将UC MSCs与活动期狼疮患者外周血单个核细胞(PBMC)共培养,观察UC MSCs增殖、凋亡及表面标志物的变化。通过真实的时间聚合酶链反应(PCR)检测UC MSC的功能分子,并通过Western blot分析其信号通路。随访狼疮患者MSC移植(MSCT)的临床效果,同时通过酶联免疫吸附试验分析基线血清细胞因子。狼疮患者外周血单个核细胞共培养可促进MSC增殖。狼疮PBMC在刺激UC MSC分泌血管内皮生长因子(VEGF)和CXCL-12方面更有效。此外,狼疮PBMC激活UC MSC中的Akt、IκB和Stat 5信号通路,但不影响Erk 1/2和Smad 1/5/8通路。此外,我们的临床研究表明,较高的IFN-γ基线水平可能预测活动性狼疮患者对MSCT的良好反应。基线IFN-γ水平可以预测活动性狼疮患者对MSC治疗的临床反应,这将有助于选择合适的患者进行临床移植。干细胞转化医学2017;6:1777-1785
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
DOI: 10.1038/srep29909
发表时间: 2016-07-25
期刊: Scientific reports
影响因子: 4.6
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