Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis
Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Mice Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis
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DOI：
10.3727/096368910x557245
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Han, Zhong Chao
中科院分区：
文献类型：
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作者：
Liang, Lu;Dong, Chunlan;Han, Zhong Chao
间充质干细胞（MSCs）具有较差的免疫原性和强大的免疫抑制活性，已成为治疗异常免疫反应引起的疾病的有希望的细胞疗法候选者。在这项研究中，我们在三硝基苯磺酸（TNBS）诱导的结肠炎模型中研究了人脐带源性间充质干细胞（hUC-MSCs）是否可以改善结肠炎。将tnbs处理的结肠炎小鼠注入hUC-MSCs或对照组。注射后第1、3、5天处死小鼠，通过体重、结肠长度和组织学分析评价小鼠的临床和病理情况。ELISA法检测结肠促炎细胞因子蛋白的表达水平。采用活体成像和免疫荧光显微镜观察hUC-MSCs的归巢情况。发现hUC-MSCs迁移到炎症结肠，有效治疗结肠炎小鼠，改善临床和病理症状。huc - msc处理小鼠结肠组织中IL-17和IL-23以及ifn - γ和IL-6的水平明显低于载药处理小鼠。共培养实验表明，hUC-MSCs不仅能抑制ifn - γ的表达，还能显著抑制结肠炎小鼠固有层单核细胞（LPMCs）、脾细胞或正常动物分离细胞在IL-23刺激下产生IL-17。系统输注hUC-MSCs可归巢炎性结肠，有效改善结肠炎。除了已知的对th1型免疫反应的抑制作用外，huc - msc介导的IL-23/IL-17调节的炎症反应在结肠炎的改善中也起着重要作用。
Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-gamma and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-gamma expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis.