Introducing the immunomodulatory effects of mesenchymal stem cells in an experimental model of Behçet’s disease

Tina Mazaheri , Abdolreza Esmaeilzadeh , Mehri H.KH. Mirzaei
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引用次数: 21

Abstract

Behçet’s disease (BD) is a systemic vasculitis which is characterised by oral, aphthous ulcers, genital ulcers, skin lesions and ocular manifestations. Although the aetiopathogenesis of BD is still unknown, the critical role of Th1 immune responses, neutrophil hyperactivation alongside overproduction of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-8, tumour necrosis factor-alpha (TNFα) and particularly IL-17 have been demonstrated in the immunopathogenesis of the disease. Despite significant progress in understanding of the aetiology of the disease, its treatment remains intricate, and is still treated with immune-suppressive drugs and biological agents with probable systemic side effects. Accordingly, there is a necessity to establish the more efficient and less toxic therapeutic methods which may offer a long-time remission of BD.

Mesenchymal stem cells (MSCs) are non-haematopoietic and multipotential stem cells with immunosuppressive capacities in innate and acquired immune systems. MSCs can migrate to damaged tissues and prevent secretion of proinflammatory cytokines and other immunomodulatory effectors, increasing the survival of damaged cells, although the exact underlying mechanisms are still unknown. For this purpose, numerous herpes simplex viruses are injected into C57BL/6 mice to produce Behçet’s mouse model and transferring a certain number of MSCs may have therapeutic value for control of Behçet’s animal model, so researchers could deliberate the function of MSCs and proinflammatory cytokines particularly IL-17A-F, TNF-α, interferon gamma (IFN-γ), IL-2, IL-6 and IL-8 in an experimental model.

The aim of this hypothesis is to evaluate immunosuppressive and immunomodulatory properties of MSCs in syngeneic animal model for BD, in order to clarify the mechanisms of MSCs in BD management, as a broad and more confident treatment in clinical application.

介绍间充质干细胞在behet病实验模型中的免疫调节作用
behet病(BD)是一种全身性血管炎,其特征是口腔溃疡、口腔溃疡、生殖器溃疡、皮肤病变和眼部表现。虽然BD的发病机制尚不清楚,但Th1免疫反应、中性粒细胞过度激活以及促炎细胞因子如白细胞介素-1 (IL-1)、IL-6、IL-8、肿瘤坏死因子α (tnf - α),特别是IL-17的过量产生在该疾病的免疫发病机制中发挥了关键作用。尽管在了解该病的病因方面取得了重大进展,但其治疗仍然复杂,并且仍然使用免疫抑制药物和可能产生全身副作用的生物制剂进行治疗。因此,有必要建立更有效、毒性更小的治疗方法,以提供长期的缓解。间充质干细胞(MSCs)是非造血和多能干细胞,在先天和获得性免疫系统中具有免疫抑制能力。MSCs可以迁移到受损组织,阻止促炎细胞因子和其他免疫调节效应物的分泌,增加受损细胞的存活率,尽管确切的潜在机制尚不清楚。为此,在C57BL/6小鼠体内注射大量单纯疱疹病毒制备behet小鼠模型,转移一定数量的MSCs可能对behet动物模型的控制具有治疗价值,因此研究人员可以在实验模型中研究MSCs与促炎细胞因子特别是IL-17A-F、TNF-α、干扰素γ (IFN-γ)、IL-2、IL-6和IL-8的功能。本假设的目的是评估MSCs在BD同系性动物模型中的免疫抑制和免疫调节特性,以阐明MSCs在BD治疗中的作用机制,使其在临床应用中更广泛、更有信心。
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