诱导性多能干细胞来源的MSCs对心跳骤停后MODS的免疫调理作用及机制研究

心跳骤停后多脏器功能不全综合征（PR-MODS）同时存在炎症反应亢进和免疫功能抑制两种病生机制，成体间充质干细胞(MSCs)可平衡调节这些异常而发挥疗效，但其来源少且效果不持久。诱导性多能干细胞可提供无限来源的MSC(iPS-MSCs)且功能更强，我们已证实其可抑制淋巴细胞增殖、下调Th1 型反应，有效清除病菌并降低PR-MODS动物病死率。因此我们设想iPS-MSCs可通过抑制炎症亢进及增强机体免疫功能、有效清除病菌而治疗PR-MODS。本课题拟从抗炎和增强免疫两个角度，从Th1/Th2/Th17/Treg、B细胞、树突细胞多个层次，利用PR-MODS患者（体外）及大鼠模型（体内）系统地探讨iPS-MSCs对其炎症免疫紊乱的调理作用，并利用基因芯片分析所涉及的各个信号通路以明了其核心机制。本研究将为iPS-MSCs对复杂炎症免疫紊乱的调理治疗提供科学根据，具有重要理论意义及临床应用价值。

The pathophysiology of post-resuscitation multiple organ dysfunction syndrome (PR-MODS) involves in both exaggerated inflammatory response and the inhibition of immune response. The mesenchyme stem cells (MSCs) derived from the adult tissues could reduce PR-MODS associated inflammation and organ dysfunction. However there are several potential limitations of using adult-MSCs such as a limited proliferative capacity and quick losing differentiation potential. Induced pluripotent stem (iPS) cells offer an unlimited source for MSCs generation. We previously found that iPS-MSCs inhibited lymphocyte proliferation, downregulated TH1 response, eliminated pathogenic bacteria and reduced the mortality rate in a rat PR-MODS model. Therefore, we hypothesize that iPS-MSCs could ameliorate PR-MODS via both inhibiting the exaggerated inflammation response and upregulating the immune function. In this study, we aim to investigate the immunomodulation of iPS-MSCs on PR-MODS in the patients (in vitro) and in the rats(in vivo). We will focus on the role of iPS-MSCs on the systemic inflammation and low immune function via evaluating the Th1/Th2/Th17/Treg cells, B cells and dendritic cells. We will further investigate the possible genes involved in the signaling pathways using microarray. This study will provide useful information to the application of iPS-MSCs to PR-MODS in clinical trails.