Immunomodulatory effect of Urine-derived Stem Cells on Inflammatory Bowel Diseases via Downregulating Th1/Th17 Immune Responses in a PGE2-dependent Manner.
Immunomodulatory effect of Urine-derived Stem Cells on Inflammatory Bowel Diseases via Downregulating Th1/Th17 Immune Responses in a PGE2-dependent Manner.
复制标题
尿源干细胞通过 PGE2 依赖性方式下调 Th1/Th17 免疫反应对炎症性肠病的免疫调节作用。
DOI：
10.1093/ecco-jcc/jjz200
复制
发表时间：
2019-12
影响因子：
8
通讯作者：
Lan Ping
中科院分区：
文献类型：
--
作者：
Zhou Chi;Wu Xian-Rui;Liu Hua-Shan;Liu Xuan-Hui;Liu Gui-Hua;Zheng Xiao-Bin;Hu Tuo;Liang Zhen-Xing;He Xiao-Wen;Wu Xiao-Jian;Smith Leona C;Zhang Yuan-Yuan;Lan Ping
背景与目的
尽管干细胞疗法在治疗炎症性肠病（IBD）方面具有治疗前景，但大多数供体细胞群必须通过侵入性方法获得，并且通常未得到充分验证。尿源性干细胞（USC）最近被证明具有再生特性，可以以安全，低成本和非侵入性的方式收获。本研究旨在评价USC的免疫调节作用及其在IBD治疗中的疗效。
方法
从健康成年男性志愿者（n=3，年龄24-30岁）的尿液中分离并扩增人USC。USC的特征在于细胞表面标志物表达谱和多能分化。通过与经植物血凝素（PHA）刺激的人CD 4 + T细胞共培养来评价USC的体外免疫调节作用。流式细胞仪检测CD 4 + T细胞增殖。细胞因子芯片和定量RT-PCR检测细胞因子水平。采用葡聚糖硫酸钠（DSS）和2，4，6-三硝基苯磺酸（TNBS）诱导的小鼠结肠炎模型，评价USC的体内治疗价值。比较USC和骨髓间充质干细胞（BMSC）与CD 4 + T细胞共培养时的免疫调节作用。比较了USC和BMSC对IBD的治疗效果。
结果
USC间充质干细胞标志物阳性，但造血干细胞标志物阴性。这些细胞分化成骨，脂肪和软骨细胞系。与BMSC相似，当与USC共培养时，CD 4 + T细胞的增殖被显著抑制，这是Th 1/Th 17免疫应答抑制的结果。在急性和慢性小鼠结肠炎模型中，全身给予USC显著改善了结肠炎的临床和组织病理学严重程度，并增加了存活率。此外，植入USC导致Th 1/Th 17免疫应答以PGE 2依赖的方式下调。
结论
该研究表明，USC的植入通过下调Th 1/Th 17免疫应答减少IBD啮齿动物模型中的炎症，表明USC疗法作为IBD的潜在基于细胞的治疗候选物。
BACKGROUND AND AIMS
Despite the therapeutic promise of stem cell therapy in the treatment of inflammatory bowel diseases (IBD), the most donor cell populations have to be obtained via invasive approaches and often remain insufficiently validated. Urine-derived stem cells (USC) were recently shown to have regenerative properties, which can be harvested in a safe, low-cost and non-invasive way. This study aims to evaluate the immunomodulatory effect of USC and its efficacy in the management of IBD.
METHODS
Human USC were isolated and expanded from the urine of healthy male adult volunteers (n=3, age arrange 24-30 years old). USC were characterized by cell surface marker expression profile and multipotent differentiation. In vitro immunomodulatory effect of USC was evaluated by co-culturing with human CD4+ T cells upon stimulation with Phytohaemagglutinin (PHA). The proliferation of CD4+ T was measured by FACS. Cytokine array and quantitative RT-PCR were applied to examine cytokine levels. In vivo therapeutic value of USC was assessed using murine colitis model induced by dextran sulfate sodium (DSS) or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The immunomodulatory effect of USC and bone marrow-derived mesenchymal stem cells (BMSC) was compared when co-cultured with CD4+ T cells. The therapeutic efficacy of USC and BMSC on IBD was compared when administrated in acute DSS model in vivo.
RESULTS
USC were positive for mesenchymal stem cell markers but were negative for hematopoietic stem cell markers. These cells differentiated into osteo-, adipo- and chondro-genic cell lineages. Similar to BMSC, the proliferation of CD4+ T cells was significantly inhibited when co-cultured with USC, as a consequence of Th1/Th17 immune response inhibition. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in both acute and chronic murine colitis models. Moreover, implantation of USC led down-regulation of the Th1/Th17 immune responses in a PGE2-dependent manner.
CONCLUSIONS
This study demonstrated that implantation of USC reduces inflammation in IBD rodent model via downregulation of Th1/Th17 immune responses, indicating that USC therapy serves as a potential cell-based therapeutic candidate for IBD.
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DOI：
10.1155/2014/928461
发表时间：
2014
期刊：
ISRN inflammation
影响因子：
--
作者：
Gálvez J
通讯作者：
Gálvez J
尿源干细胞对鱼精蛋白/脂多糖诱导的间质性膀胱炎大鼠模型的治疗作用
影响因子：
7.5
作者：
Li J;Luo H;Dong X;Liu Q;Wu C;Zhang T;Hu X;Zhang Y;Song B;Li L
通讯作者：
Li L
影响因子：
11
作者：
Wang LT;Ting CH;Yen ML;Liu KJ;Sytwu HK;Wu KK;Yen BL
通讯作者：
Yen BL
影响因子：
82.9
作者：
通讯作者：
--
DOI：
--
发表时间：
1995
期刊：
The American journal of gastroenterology
影响因子：
--
作者：
B. Greenwald;S. James
通讯作者：
B. Greenwald;S. James