间充质干细胞（MSCs）移植治疗肝硬化有很好的治疗效果和潜力，但其治疗机制不明，限制了更好的临床应用和推广。我们前期研究发现：①MSCs可有效治疗小鼠肝硬化；②MSCs治疗后小鼠体内TSG-6明显升高，且与治疗效果相关；③初步证实TSG-6具有一定的抗炎作用，发挥作用必须与巨噬细胞表面的CD44受体结合；④MSCs治疗后巨噬细胞表型由M1型转换为M2型。据此推测：MSCs分泌的抗炎因子TSG-6可能通过调控巨噬细胞极化类型改善肝硬化。本课题拟利用TSG-6基因敲减的MSCs及重组TSG-6蛋白治疗肝硬化小鼠，从正反两方面进一步研究TSG-6在肝硬化治疗中的作用；通过流式、ELISA、免疫荧光等体内及体外实验明确TSG-6对巨噬细胞极化类型的影响；同时探讨TSG-6调控巨噬细胞极化类型的信号转导通路。研究结果不仅有助于阐明干细胞治疗肝硬化的分子机理，更为细胞因子临床治疗肝硬化提供全新的思路。

Mesenchymal stem cells (MSCs) transplantation for the treatment of liver cirrhosis has a good therapeutic effect and potential, but the complex mechanism is far from being understood, limiting the better clinical application. In the previous study, we found that MSCs can treat cirrhotic mice effectively and TSG-6 is significantly increased after the treatment. The concentration of TSG-6 was related to the therapeutic effect. In addition, we demonstrated that TSG-6 was an anti-inflammatory factor and depended on the expression of CD44 on macrophages. Furthermore, macrophage phenotype was conversed from M1 to M2 after MSCs treatment. Thus, we hypothesized that the anti-inflammatory factor TSG-6 secreted by MSCs alleviate liver cirrhosis may via regulating macrophages from M1 to M2 phenotype. In this study, we are going to explore the role of TSG-6 in the treatment of cirrhosis using the TSG-6 gene knockout MSCs and recombinant TSG-6 protein. We also study the effect of TSG-6 on macrophage phenotype in vitro and in vivo. In addition, the signal transduction pathway of TSG-6-regulated macrophage polarization was explored. This study not only help to clarify the molecular mechanism of stem cell therapy for liver cirrhosis, but also provide a new idea for the clinical treatment of liver cirrhosis by cytokine therapy.