Stem Cell Biology, Haematology Centre, Department of Medicine, Imperial College, London, UK.
Best Pract Res Clin Haematol. 2011 Mar;24(1):49-57. doi: 10.1016/j.beha.2011.01.002. Epub 2011 Feb 23.
Mesenchymal stem cell (MSC) immunosuppressive properties offer a potentially attractive therapeutic modality for autoimmune diseases. MSC inhibit virtually all types of immune responses in vitro and prevent the induction of disease in several experimental models of autoimmunity. However, the processes involved in the pathogenesis of human diseases are more complicated and treatment cannot be administered before disease induction. In autoimmune diseases persistent antigenic stimulation recruits endogenous MSC to the site of lesion that contribute to the fibrotic evolution. Therefore, administering MSC to a chronic inflammatory disorder may not be desirable. In fact, MSC are not constitutively immunosuppressive but require a 'licensing' step provided by molecules of acute phase inflammation, like IFNγ and TNF-α, or toll-like receptor (TLR) ligands. Conversely, different cytokines and/or the stimulation of selective TLR make MSC to become immunostimulatory. Therefore, dissecting the inflammatory environment in autoimmune diseases will identify the best conditions amenable to successful MSC therapy.
间充质干细胞(MSC)的免疫抑制特性为自身免疫性疾病提供了一种有吸引力的潜在治疗方法。MSC 在体外抑制几乎所有类型的免疫反应,并在几种自身免疫性疾病的实验模型中预防疾病的诱导。然而,人类疾病发病机制中涉及的过程更加复杂,并且在疾病诱导之前不能进行治疗。在自身免疫性疾病中,持续的抗原刺激会招募内源性 MSC 到病变部位,从而促进纤维化的演变。因此,向慢性炎症性疾病中给予 MSC 可能不是理想的。事实上,MSC 不是固有免疫抑制的,但需要急性炎症分子(如 IFNγ 和 TNF-α)或 Toll 样受体(TLR)配体提供的“许可”步骤。相反,不同的细胞因子和/或选择性 TLR 的刺激使 MSC 成为免疫刺激性的。因此,解析自身免疫性疾病中的炎症环境将确定最适合 MSC 治疗成功的条件。