Mishra Abhay Prakash, Kumar Rajesh, Harilal Seetha, Nigam Manisha, Datta Deepanjan, Singh Sudarshan
Department of Pharmacology, University of Free State, Bloemfontein 9301, South Africa.
Department of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
ACS Pharmacol Transl Sci. 2024 Jul 18;7(8):2280-2305. doi: 10.1021/acsptsci.4c00260. eCollection 2024 Aug 9.
Rheumatoid arthritis (RA) is a complex condition that is influenced by various causes, including immunological, genetic, and environmental factors. Several studies using animal models have documented immune system dysfunction and described the clinical characteristics of the disease. These studies have provided valuable insights into the pathogenesis of inflammatory arthritis and the identification of new targets for treatment. Nevertheless, none of these animal models successfully replicated all the characteristics of RA. Additionally, numerous experimental medications, which were developed based on our enhanced comprehension of the immune system's function in RA, have shown potential in animal research but ultimately proved ineffective during different stages of clinical trials. There have been several novel therapy alternatives, which do not achieve a consistently outstanding therapeutic outcome in all patients. This underscores the importance of employing the progress in models, particularly 3D models like tissue explants, and diverse multicomponent approaches such as coculture strategies, synovial membrane, articular cartilage, and subchondral bone models that accurately replicate the structural characteristics of RA pathophysiology. These methods are crucial for the advancement of potential therapeutic strategies. This review discusses the latest advancements in models and their potential to greatly impact research on managing RA.
类风湿性关节炎(RA)是一种复杂的病症,受多种因素影响,包括免疫、遗传和环境因素。多项使用动物模型的研究记录了免疫系统功能障碍,并描述了该疾病的临床特征。这些研究为炎性关节炎的发病机制及新治疗靶点的识别提供了宝贵见解。然而,这些动物模型均未成功复制RA的所有特征。此外,基于我们对RA中免疫系统功能的深入理解而研发的众多实验性药物,在动物研究中显示出潜力,但最终在临床试验的不同阶段被证明无效。有几种新型治疗方案,在所有患者中并未都取得始终出色的治疗效果。这凸显了采用模型方面的进展的重要性,特别是像组织外植体这样的3D模型,以及多种多组分方法,如共培养策略、滑膜、关节软骨和软骨下骨模型,这些能准确复制RA病理生理学的结构特征。这些方法对于潜在治疗策略的推进至关重要。本综述讨论了模型方面的最新进展及其对RA管理研究产生重大影响的潜力。