抑制炎症介质增强MSC修复炎症性肠病粘膜损伤的研究

项目名称： 抑制炎症介质增强MSC修复炎症性肠病粘膜损伤的研究

项目编号： No.81200332

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 练磊

作者单位： 中山大学

项目金额： 23万元

中文摘要： 炎症性肠病（IBD）存在肠道粘膜上皮损伤以及粘膜免疫微环境紊乱，呈不可控的慢性持续性炎症过程。研究表明间充质干细胞（MSC）可分化为肠道上皮细胞修复粘膜损伤以及调节粘膜免疫，已成为IBD治疗的又一手段。然而MSC在体内凋亡迅速、生存时间短，严重限制其临床应用。2011年Nature Medicine文章认为TNF-α及 IFN-γ等炎症介质表达水平与MSC体内凋亡呈正相关并抑制其成骨能力。我们前期的研究证实TNF-α等炎症介质在IBD小鼠模型体内高表达，那么这些炎症介质是否为限制MSC发挥临床疗效的关键因素？本课题组拟在前期研究的基础上，继续探讨TNF-α等炎症介质对MSC体外存活及向上皮转化的影响；同时，通过体内干预TNF-α等炎症介质的水平，观察MSC治疗IBD的疗效变化并进行相关机制探讨。

中文关键词： 炎症性肠病；间充质干细胞；炎症因子；疗效；机制

英文摘要： Mucosal injury and disturbance in mucosal immunity has been demonstrated in the inflammation involved in IBD, which presents as uncontrollable, persistent, and chronic inflammatory process. Conventional medical therapy cannot alter such a complex network. MSC can home to site of injury, modulate mucosal immunity, and repair mucosal injury, leading to significant clinical improvement in patients with IBD. However, the outcome after MSC treatment is limited. Inflammatory cytokines including TNF-a and IFN-γ are shown to enhance osteogenesis in Nature Medicine in 2011. Therefore, we aim to investigate factors associated with outcomes after MSC administration, and determin whether aspirin and Treg can augment the outcome after MSC treatment using IBD animal models. This study can reveal the mechanism invovled in the treatment of MSC in IBD and explore interventional methods to enchance the MSC treatment outcomes.

英文关键词： Inflammatory Bowel Disease；Mesenchymal stem cells；Inflammatory cytokines；Efficacy；Mechanism