Advanced Translational Diagnostics Laboratory, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste 34137, Italy.
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34127, Italy.
World J Gastroenterol. 2022 Jun 28;28(24):2636-2653. doi: 10.3748/wjg.v28.i24.2636.
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract that have emerged as a growing problem in industrialized countries. Knowledge of IBD pathogenesis is still incomplete, and the most widely-accepted interpretation considers genetic factors, environmental stimuli, uncontrolled immune responses and altered intestinal microbiota composition as determinants of IBD, leading to dysfunction of the intestinal epithelial functions. models commonly used to study the intestinal barrier do not fully reflect the proper intestinal architecture. An important innovation is represented by organoids, 3D cell structures derived from stem cells that can self-organize into functional organ-specific structures. Organoids may be generated from induced pluripotent stem cells or adult intestinal stem cells of IBD patients and therefore retain their genetic and transcriptomic profile. These models are powerful pharmacological tools to better understand IBD pathogenesis, to study the mechanisms of action on the epithelial barrier of drugs already used in the treatment of IBD, and to evaluate novel target-directed molecules which could improve therapeutic strategies. The aim of this review is to illustrate the potential use of organoids for therapy personalization by focusing on the most significant advances in IBD research achieved through the use of adult stem cells-derived intestinal organoids.
炎症性肠病(IBD)是一种慢性肠道炎症性疾病,在工业化国家已成为一个日益严重的问题。IBD 的发病机制知识仍不完整,最广泛接受的解释认为遗传因素、环境刺激、免疫反应失控和肠道微生物群落组成的改变是 IBD 的决定因素,导致肠道上皮功能障碍。目前常用于研究肠道屏障的模型不能完全反映正常的肠道结构。一个重要的创新是类器官,它是源自干细胞的 3D 细胞结构,可以自我组织成具有特定功能的器官特异性结构。类器官可以从诱导多能干细胞或 IBD 患者的成人肠道干细胞中产生,因此保留了它们的遗传和转录组特征。这些模型是更好地理解 IBD 发病机制的强大药理学工具,可用于研究已用于治疗 IBD 的药物对上皮屏障作用的机制,并评估可能改善治疗策略的新型靶向分子。本文的目的是通过重点介绍使用成人干细胞衍生的肠道类器官在 IBD 研究中取得的最显著进展,说明类器官在治疗个体化方面的潜在用途。