El-Badri Nagwa S, Hakki Amal, Ferrari Annabella, Shamekh Rania, Good Robert A
Department of Neurosurgery--Center of Excellence for Aging and Brain Repair, MDC 78, College of Medicine University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA.
Immunol Res. 2008;41(1):79-86. doi: 10.1007/s12026-007-0053-8.
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease that involves several vital organs including the cardiovascular system, joints, and kidneys. The pathology is characterized by accumulation of autoreactive lymphocytes that attack the patients' own tissues, secretion of autoantibodies and deposition of immune complexes in vital organs. Chronic widespread inflammation is the hallmark of SLE and the target of current therapy. According to recent theories, intonating immune circuits of inflammatory cytokines and immune cells constitute highly specialized targets for SLE therapy, which nonetheless consists for the most part of anti-inflammatory medications and cytotoxic drugs. For advanced autoimmune disorders, cell therapy aiming at introducing "healthy" stem cells has been promising, keeping in mind that in its current state, stem cell therapy is reserved for the most advanced diseases refractory to traditional therapy. Ongoing studies in our laboratories examined the role of the bone marrow microenvironment, in particular, mesenchymal stem cells (MSCs) in the etiopathogenesis of SLE. Specifically, we are testing the hypothesis that, in human SLE mouse model, marrow MSCs are defective structurally and functionally. Preliminary data indicate that structural and functional defects in MSC population from an autoimmune mouse model for human SLE may contribute to this pathology and consequently present a target for cell therapy.
系统性红斑狼疮（SLE）是一种常见的系统性自身免疫性疾病，累及包括心血管系统、关节和肾脏在内的多个重要器官。其病理特征为自身反应性淋巴细胞积聚，攻击患者自身组织，自身抗体分泌以及免疫复合物在重要器官中沉积。慢性广泛炎症是SLE的标志，也是当前治疗的靶点。根据最新理论，调节炎性细胞因子和免疫细胞的免疫回路构成了SLE治疗的高度专业化靶点，然而目前的治疗大多由抗炎药物和细胞毒性药物组成。对于晚期自身免疫性疾病，旨在引入“健康”干细胞的细胞治疗已显示出前景，但要记住，就目前的状态而言，干细胞治疗仅适用于对传统治疗难治的最晚期疾病。我们实验室正在进行的研究探讨了骨髓微环境，特别是间充质干细胞（MSC）在SLE发病机制中的作用。具体而言，我们正在检验这样一个假设：在人类SLE小鼠模型中，骨髓MSC在结构和功能上存在缺陷。初步数据表明，来自人类SLE自身免疫小鼠模型的MSC群体的结构和功能缺陷可能导致这种病理状况，因此成为细胞治疗的一个靶点。
