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Innovative human-specific investigational approaches to autoimmune disease

机译：自身免疫疾病的创新性的人体特异性调查方法

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Autoimmune diseases are exclusively human diseases with a complex genetic background and variable clinical presentation, of which the underlying pathophysiology is insufficiently understood. Current treatment is mainly empirical with limited efficacy and significant side effects. To develop more effective targeted therapy for personalized treatment, understanding of the human pathophysiology is crucial, implying a high need for human investigational disease models. Using the example of anti-neutrophil cytoplasmic antibody (ANCA) autoimmune vasculitis, the concept of building an in vitro organ-on-chip type human disease model, consisting of cultured organ-specific vascular tissue in interaction with relevant immune system components (e.g. lymph node and thymus tissue) is presented. This in vitro approach makes use of advances in engineering and human stem cell technologies, enabling derivation of pluripotent stem cell lines from patients, differentiation to required cell types, and incorporation in microfluidic chip-based culture systems to optimally mimic in vivo disease conditions. Knowledge-based computational disease modeling is introduced as a valuable complementary tool to generate an integral mechanistic picture of the disease. Combining these multidisciplinary developments promises breakthroughs in understanding autoimmune disease and targeted drug development, while simultaneously reducing use of animal models. Current state of the art and issues remaining to be solved are discussed.
机译：自身免疫性疾病仅具有复杂的遗传背景和可变临床介绍的人类疾病，其中潜在的病理生理学不够理解。目前的治疗主要具有有限的疗效和显着的副作用。为了为个性化待遇开发更有效的目标治疗，对人类病理生理学的理解至关重要，暗示对人类调查疾病模型的高度需求。使用抗中性粒细胞细胞质抗体（ANCA）自身免疫血管炎，构建体外运动器型人类疾病模型的概念，由培养的器官特异性血管组织与相关免疫系统组分相互作用（例如淋巴提出了节点和胸腺组织。这种体外方法利用工程和人类干细胞技术的进步，从患者中衍生多能干细胞系，与所需细胞类型的分化，并掺入基于微流体芯片的培养系统，以在体内疾病病症中最佳地模拟。基于知识的计算疾病建模被引入为有价值的互补工具，以产生疾病的一个整体机制图片。结合这些多学科发展，承诺在了解自身免疫疾病和有针对性的药物开发方面的突破，同时减少了动物模型的使用。讨论了现有技术和留下的问题待解决的问题。

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