Modeling Rheumatoid Arthritis In Vitro: From Experimental Feasibility to Physiological Proximity.
Modeling Rheumatoid Arthritis In Vitro: From Experimental Feasibility to Physiological Proximity.
复制标题
风湿性关节炎体外建模：从实验可行性到生理接近性。
DOI：
10.3390/ijms21217916
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发表时间：
2020-10-25
影响因子：
5.6
通讯作者：
Gaber T
中科院分区：
文献类型：
--
作者：
Damerau A;Gaber T
风湿性关节炎（RA）是一种慢性、炎性和全身性自身免疫性疾病，其影响结缔组织，主要是关节。如果不治疗，RA最终导致进行性软骨和骨退化。RA发病机制的病因学尚不清楚，其临床表现具有异质性，并且与针对修饰的自身表位的自身抗体相关。虽然已经存在许多用于临床前研究的RA模型，但许多当前的关节炎模型系统具有有限的预测价值，因为它们要么基于遗传学上遥远起源的动物，要么遭受过度简化的体外培养条件。这些局限性对临床前研究和临床翻译提出了相当大的挑战。因此，一个复杂的实验性的人为基础的体外方法模拟RA是必不可少的（i）研究人类RA的发病机制的关键机制，（ii）确定新的治疗方法的目标，（iii）测试这些方法，（iv）促进临床结果的可转移性，（v）减少实验室动物的使用。在这里，我们总结了最常用的RA体外模型，并讨论了它们的实验可行性和生理接近人类RA的病理生理学，以突出新的人类为基础的途径在RA研究，以增加我们对人类病理生理学的知识，并开发有效的靶向治疗。
Rheumatoid arthritis (RA) is a chronic, inflammatory, and systemic autoimmune disease that affects the connective tissue and primarily the joints. If not treated, RA ultimately leads to progressive cartilage and bone degeneration. The etiology of the pathogenesis of RA is unknown, demonstrating heterogeneity in its clinical presentation, and is associated with autoantibodies directed against modified self-epitopes. Although many models already exist for RA for preclinical research, many current model systems of arthritis have limited predictive value because they are either based on animals of phylogenetically distant origin or suffer from overly simplified in vitro culture conditions. These limitations pose considerable challenges for preclinical research and therefore clinical translation. Thus, a sophisticated experimental human-based in vitro approach mimicking RA is essential to (i) investigate key mechanisms in the pathogenesis of human RA, (ii) identify targets for new therapeutic approaches, (iii) test these approaches, (iv) facilitate the clinical transferability of results, and (v) reduce the use of laboratory animals. Here, we summarize the most commonly used in vitro models of RA and discuss their experimental feasibility and physiological proximity to the pathophysiology of human RA to highlight new human-based avenues in RA research to increase our knowledge on human pathophysiology and develop effective targeted therapies.
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