Simpson Hanna L, Smits Eline, Moerkens Renée, Wijmenga Cisca, Mooiweer Joram, Jonkers Iris H, Withoff Sebo
Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Trends Mol Med. 2025 Feb;31(2):117-137. doi: 10.1016/j.molmed.2024.10.003. Epub 2024 Oct 23.
Coeliac disease (CeD) is an immune-mediated disorder characterised by gluten-triggered inflammation and damage in the small intestine, with lifelong gluten-free diet (GFD) as the only treatment. It is a multifactorial disease, involving genetic and environmental susceptibility factors, and its complexity and lack of comprehensive human model systems have hindered understanding of its pathogenesis and development of new treatments. Therefore, it is crucial to establish systems that recapitulate patient genetic background and the interactions between the small intestinal epithelial barrier, immune cells, and environment that contribute to CeD. In this review, we discuss disease complexity, recent advances in stem cell biology, organoids, tissue co-cultures, and organ-on-chip (OoC) systems that facilitate the development of comprehensive human model systems, and model applications in preclinical studies of potential treatments.
乳糜泻（CeD）是一种免疫介导的疾病，其特征是麸质引发小肠炎症和损伤，终身无麸质饮食（GFD）是唯一的治疗方法。它是一种多因素疾病，涉及遗传和环境易感性因素，其复杂性以及缺乏全面的人体模型系统阻碍了对其发病机制的理解和新治疗方法的开发。因此，建立能够概括患者遗传背景以及有助于乳糜泻的小肠上皮屏障、免疫细胞和环境之间相互作用的系统至关重要。在这篇综述中，我们讨论了疾病的复杂性、干细胞生物学、类器官、组织共培养和芯片器官（OoC）系统的最新进展，这些进展有助于开发全面的人体模型系统，以及在潜在治疗方法临床前研究中的模型应用。
