间充质干细胞移植可能通过重建免疫耐受而治疗风湿病

      摘要（英国）： 免疫耐受对防止自身免疫病和保持免疫稳定很关键，随着对细胞因子网络的深入了解，类风湿关节炎治疗中已引入了抗TNFα、IL-1和IL-6信号的中和抗体，但仍有一些患者对这些药无效，病情不能达完全缓解。间充质干细胞对破坏的关节组织如软骨、骨和肌腱有修复作用，在体内外还有强大的抗炎和免疫调节作用，其治疗克罗恩病、I型糖尿病、移植物抗宿主疾病及多发性硬化已进行了II期和II期临床研究。间充质干细胞在自身免疫性风湿病(尤其是类风湿关节炎的胶原诱导性关节炎模型鼠)中的疗效有一定矛盾，而在狼疮鼠模型中的疗效虽有矛盾，但最近报道治疗系统性红斑狼疮的疗效良好。本文我们探讨了间充质干细胞移植作为类风湿关节炎、系统性红斑狼疮和系统性硬化症细胞治疗的可能性，分析了结果矛盾的可能原因。我们也强调间充质干细胞功能异常可能在这些疾病发病中发挥了作用，最后，我们将在细胞水平探讨间充质干细胞发挥疗效的可能机制，包括对调节T细胞和Th17细胞的作用。北京大学第三医院风湿免疫科刘湘源

     附原文  Abstract  Immunological tolerance is critical in preventing autoimmune disease and maintaining immune homeostasis. Increased understanding regarding cytokine networks led to the development of neutralizing antibodies against TNF alpha, IL-1 and IL-6 signalling in the treatment of rheumatoid arthritis (RA). However, there remains an unmet need given the significant number of patients not achieving remission nor responding to these drugs. Mesenchymal (stromal) stem cells (MSCs) are promising tools for the repair of damaged joint tissues such as cartilage, bone and tendons. They also have potent anti-inflammatory and immunomodulatory properties both in vitro and in vivo [1]. Research into MSC therapy for Crohn"s disease, type I diabetes, graft-versus-host disease (GvHD) and multiple sclerosis continues apace with phase II/III trials ongoing (www.clinicaltrials.gov). There have been conflicting reports regarding their effects in the autoimmune rheumatic diseases, particularly in the collagen-induced arthritis mouse model of RA [2-8]. Conversely, promising results in patients with systemic lupus erythematosus (SLE) were recently reported [9] even in the face of conflicting results in murine models of SLE. In this article we will examine MSCs as a possible cellular therapy for RA, SLE and systemic sclerosis (SSc) and critically review possible reasons for conflicting results in the literature. We will also address whether MSC dysfunction could play a role in the aetiopathogenesis of these conditions. Finally, we will examine the possible mechanisms of MSCs at a cellular level including the effects on regulatory T (Treg) cells and type 17 T helper (Th17) cell populations.

     引自：Macdonald GI, Augello A, De Bari C. Mesenchymal stem cells: Re-establishing immunological tolerance in autoimmune rheumatic diseases. Arthritis Rheum, 2011 Jun 6. doi: 10.1002/art.30474. [Epub ahead of print]