Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
Inflamm Bowel Dis. 2018 Nov 29;24(12):2501-2509. doi: 10.1093/ibd/izy275.
Inflammatory bowel disease (IBD) is a chronic remitting disorder with increasing incidence worldwide. The intestinal epithelial barrier plays a major role in IBD, contributing to its pathogenesis, evolution, and perpetuation over time. Until recently, studies focused on exploring the role of the intestinal epithelium in IBD were hampered by the lack of techniques for the long-term culturing of human primary epithelial cells ex vivo. Recently, however, a methodology for generating stable human 3D epithelial cultures directly from adult intestinal stem cells was established. These long-term cultures, called organoids, mimic the tissue of origin and can be generated from small-size intestinal tissue samples, making it a promising tool for modeling the course of IBD.In this review, we provide an overview of the versatility of human organoid cultures in IBD modeling. We discuss recent advances and current limitations in the application of this tool for modeling the contribution of the intestinal epithelium alone and in combination with other key cellular and molecular players in the context of IBD pathophysiology. Finally, we outline the pressing need for technically standardizing the laboratory manipulation of human epithelial organoids for their broader implementation in clinically oriented IBD studies.
炎症性肠病(IBD)是一种慢性缓解性疾病,其发病率在全球范围内呈上升趋势。肠道上皮屏障在 IBD 中起着重要作用,有助于其发病机制、演变和长期持续。直到最近,由于缺乏长期体外培养人原代上皮细胞的技术,研究人员对探索肠道上皮在 IBD 中的作用的研究受到了阻碍。然而,最近建立了一种从成人肠干细胞中直接生成稳定的人 3D 上皮培养物的方法。这些长期培养物称为类器官,可模拟组织起源,并且可以从小肠组织样本中生成,因此是一种很有前途的建模 IBD 过程的工具。在这篇综述中,我们概述了人源类器官培养在 IBD 建模中的多功能性。我们讨论了该工具在单独建模肠道上皮以及结合 IBD 病理生理学中其他关键细胞和分子成分方面的应用的最新进展和当前限制。最后,我们概述了迫切需要在技术上标准化人上皮类器官的实验室操作,以将其更广泛地应用于以临床为导向的 IBD 研究中。