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基于细胞的干预措施以阻止 1 型糖尿病中的自身免疫。

Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus.

机构信息

Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET, Instituto Partner de la Sociedad Max Planck, Buenos Aires.

出版信息

Clin Exp Immunol. 2013 Feb;171(2):135-46. doi: 10.1111/cei.12019.

Abstract

Type 1 diabetes mellitus (T1DM) results from death of insulin-secreting β cells mediated by self-immune cells, and the consequent inability of the body to maintain insulin levels for appropriate glucose homeostasis. Probably initiated by environmental factors, this disease takes place in genetically predisposed individuals. Given the autoimmune nature of T1DM, therapeutics targeting immune cells involved in disease progress have been explored over the last decade. Several high-cost trials have been attempted to prevent and/or reverse T1DM. Although a definitive solution to cure T1DM is not yet available, a large amount of information about its nature and development has contributed greatly to both the improvement of patient's health care and design of new treatments. In this study, we discuss the role of different types of immune cells involved in T1DM pathogenesis and their therapeutic potential as targets and/or modified tools to treat patients. Recently, encouraging results and new approaches to sustain remnant β cell mass and to increase β cell proliferation by different cell-based means have emerged. Results coming from ongoing clinical trials employing cell therapy designed to arrest T1DM will probably proliferate in the next few years. Strategies under consideration include infusion of several types of stem cells, dendritic cells and regulatory T cells, either manipulated genetically ex vivo or non-manipulated. Their use in combination approaches is another therapeutic alternative. Cell-based interventions, without undesirable side effects, directed to block the uncontrollable autoimmune response may become a clinical reality in the next few years for the treatment of patients with T1DM.

摘要

1 型糖尿病(T1DM)是由自身免疫细胞介导的胰岛素分泌β细胞死亡引起的,导致身体无法维持适当的葡萄糖稳态所需的胰岛素水平。这种疾病可能由环境因素引发,发生在遗传易感性个体中。鉴于 T1DM 的自身免疫性质,过去十年中一直在探索针对参与疾病进展的免疫细胞的治疗方法。已经尝试了几项高成本试验来预防和/或逆转 T1DM。尽管尚未找到治愈 T1DM 的明确方法,但大量关于其性质和发展的信息极大地促进了患者医疗保健的改善和新治疗方法的设计。在这项研究中,我们讨论了参与 T1DM 发病机制的不同类型免疫细胞的作用及其作为治疗靶点和/或改良工具的治疗潜力。最近,通过不同的基于细胞的方法维持残余β细胞量和增加β细胞增殖的令人鼓舞的结果和新方法已经出现。通过细胞疗法设计来阻止 T1DM 的正在进行的临床试验的结果可能在未来几年内会增加。正在考虑的策略包括输注几种类型的干细胞、树突状细胞和调节性 T 细胞,无论是体外遗传修饰还是非修饰。它们联合应用是另一种治疗选择。针对阻断不可控自身免疫反应的无不良副作用的基于细胞的干预措施可能在未来几年内成为治疗 T1DM 患者的临床现实。

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