间充质干细胞在炎症性疾病治疗中的基础研究和临床应用

Immunoregulatory Mechanisms and Applications of Mesenchymal Stem/Stromal Cells in Inflammatory Diseases

间充质干细胞/基质细胞(mesenchymal stem/stromal cells, MSCs),由于其独特的免疫调节能力而备受关注。在治疗克罗恩病、移植物抗宿主病、系统性红斑狼疮以及器官纤维化等炎症性疾病的临床研究和应用中, MSCs均被报道可以抑制炎症,缓解疾病进展,展现出了良好的药用前景。MSCs调控炎症微环境、改善疾病的方式有很多,总体而言,在强烈炎症因子的刺激下, MSCs可以重塑组织微环境,使之向有利于再生和免疫正常化的方向转变。机制上,在炎症因子的刺激下,MSCs通过产生免疫抑制分子、生长因子、趋化因子、补体以及代谢产物等,调控多种免疫细胞的迁移、增殖和活化等生物过程以达到调控炎症微环境的目的。更新的报道甚至提出凋亡的MSCs也能发挥免疫抑制的功能。此外, MSCs的免疫调节能力受炎症因子调控,不是与生俱来又一成不变的,因此,依据微环境中炎症因子的种类、水平, MSCs的免疫调节功能也会发生变化。该文主要总结了近年来人们对MSCs免疫调节机制、MSCs与炎症微环境相互作用的理解以及应用MSCs治疗炎症性疾病的临床现状。

Mesenchymal stem/stromal cells(MSCs)have attracted much attention due to their unique properties in immunoregulation.It has been reported that MSCs possess encouraging therapeutic potentials in treating various inflammatory diseases including inflammatory bowel disease,graft-versus-host disease,systemic lupus erythematous and organ fibrosis.MSCs employ multiple mechanisms to regulate inflammatory microenvironment.In general,MSCs are thought to enable the remodeling damaged tissue microenvironment to a more regenerative one by suppressing vigorous inflammation and secreting growth factors.Mechanically,in the presence of inflammatory mediators,MSCs regulate various immunological processes including immune cell migration,proliferation and function through the production of immunosuppressive factors,growth factors,chemokines and metabolites.Recent reports even propose that apoptotic MSCs can be immunosuppressive.As the immunomodulatory capabilities of MSCs are not constitutive but rather are determined by inflammatory cytokines,MSCs function can vary depending on the levels and types of inflammation.Here,we summarize the current understanding of MSC-mediated immunoregulation and their interactions with surrounding microenvironments.We also discuss the advances of MSC-based therapies and related issues in treating inflammatory diseases clinically.