Dazzi Francesco, van Laar Jacob M, Cope Andrew, Tyndall Alan
Stem Cell Biology Section, Kennedy Institute of Rheumatology, Imperial College Faculty of Medicine, London, UK.
Arthritis Res Ther. 2007;9(2):206. doi: 10.1186/ar2128.
Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases.
细胞疗法最初是以骨髓移植的形式用于治疗恶性肿瘤,随后在自身免疫性疾病中得到了测试并成功应用。自体造血干细胞移植(HSCT)已成为治疗预后极差的疾病(如严重硬皮病、多发性硬化症和狼疮等,在这些疾病中靶向治疗几乎无效或根本无效)的一种治愈性选择。预处理方案的改进实际上已消除了与移植相关的死亡率,从而使HSCT成为一种相对安全的选择。尽管HSCT仍然是一种非特异性方法,但在该领域所获得的知识已引领了新途径的发现。事实上,已经很明显,HSCT的治疗效果不仅仅是高剂量免疫抑制的结果,而是自身免疫性疾病潜在的异常免疫调节得以重置的结果。专业和非专业免疫抑制细胞及其生物学特性的鉴定正引发人们对其临床应用的极大兴趣。调节性T细胞在几种自身免疫性疾病中被发现异常,已被认为是实现长期缓解的关键。最近研究表明,骨髓来源的间充质干细胞不仅能够分化为多种组织,而且还能发挥强大的抗增殖作用,从而抑制免疫反应并延长造血干细胞的存活时间。所有这些潜在资源显然需要在临床前水平进行研究,但为自身免疫性疾病的细胞疗法带来了极大的热情。