本研究将应用两种新型细胞治疗手段：使用siRNA诱导的耐受树突状细胞（Tol-DC）和体外修饰的间充质干细胞（MSC）治疗类风湿关节炎。我们的前期研究发现，siRNA可以诱导产生Tol-DC，应用Tol-DC进行免疫治疗可以诱导抗原特异性的免疫耐受；MSC具有抗炎和再生功能。因为，我们推测联合使用Tol-DC和MSC进行免疫治疗具有协同/增效作用。本研究将建立一种治疗类风湿关节炎的新的免疫治疗方法，即利用CIA模型，通过联合使用Tol-DC（调整免疫应答）和MSC（促进组织再生）的策略治疗类风湿关节炎，并探讨Tol-DC和MSC的联合使用对类风湿关节炎的协同治疗作用及其细胞与分子机制。迄今为止，联合使用再生和免疫调控的方法来治疗类风湿关节炎的研究尚未见报道。

This proposal takes advantage of two types of specialized cells: Tol-DCs that suppress the immune response, and MSCs that repair the damaged joint. We hypothesize that combining the use of MSCs in conjunction with Tol-DCs will result in a synergistic therapeutic effect on Rheumatoid Arthritis through decreasing ongoing immunological attack while concurrently inducing tissue regeneration. The unique and innovative aspects of this study lie in the exploration of several modifications of MSC-based treatment through the use of gene-silenced Tol-DCs. While gene silenced DCs accelerate the induction of antigen-specific tolerance in autoimmunity, MSCs possess the capacity for regeneration and repair of damaged joints. The success of this study may lead to development of new combined MSC- and DC-based therapies for the treatment of autoimmune arthritis.