In Julie G, Foulke-Abel Jennifer, Estes Mary K, Zachos Nicholas C, Kovbasnjuk Olga, Donowitz Mark
Department of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Nat Rev Gastroenterol Hepatol. 2016 Nov;13(11):633-642. doi: 10.1038/nrgastro.2016.142. Epub 2016 Sep 28.
The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5 intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.
无限增殖的人类“迷你肠道”的发展推动了与转运生理学、发育生物学、药理学和病理生理学相关的胃肠研究的快速进展。这些迷你肠道，也称为肠类器官或结肠类器官，源自从小肠或结肠分离的LGR5肠道干细胞。添加WNT3A和其他生长因子可促进干性，并产生具有活力、生理功能的人类肠道或结肠培养物，这些培养物会形成隐窝-绒毛轴，并且可以分化为所有肠道上皮细胞类型。使用人类肠类器官进行研究的成功凸显了使用动物或体外癌症衍生细胞系来模拟转运生理学和病理生理学的局限性。例如，急性肠道感染的治疗或预防疗法一直很有限，主要是因为缺乏生理性人类肠道模型。然而，人类肠类器官模型能够对每个肠道段的分泌和吸收进行特定的功能研究，以及观察肠道感染期间发生的最早分子事件。本综述描述了将这些人类迷你肠道表征为研究肠道转运和宿主-病原体相互作用的生理模型的研究。
