Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Cell Mol Gastroenterol Hepatol. 2021;12(2):769-782. doi: 10.1016/j.jcmgh.2021.04.010. Epub 2021 Apr 22.
Intestinal organoids have become indispensable tools for many gastrointestinal researchers, advancing their studies of nontransformed intestinal epithelial cells, and their roles in an array of diseases, including inflammatory bowel disease and colon cancer. In many cases. these diseases, as well as many enteric infections, reflect pathogenic interactions between bacteria and the gut epithelium. The complexity of studying this microbe-epithelial interface in vivo has led to significant focus on modeling this cross-talk using organoid models. Considering how quickly the organoid field is advancing, it can be difficult to keep up to date with the latest techniques, as well as their respective strengths and weaknesses. This review addresses the advantages of using organoids derived from adult stem cells and the recently identified differences that biopsy location and patient age can have on organoids and their interactions with microbes. Several approaches to introducing bacteria in a relevant (apical) manner (ie, microinjecting 3-dimensional spheroids, polarity-reversed organoids, and 2-dimensional monolayers) also are addressed, as are the key readouts that can be obtained using these models. Lastly, the potential for new approaches, such as air-liquid interface, to facilitate studying bacterial interactions with important but understudied epithelial subsets such as goblet cells and their products, is evaluated.
肠类器官已成为许多胃肠道研究人员不可或缺的工具，推动了他们对未转化的肠上皮细胞的研究，以及这些细胞在一系列疾病中的作用，包括炎症性肠病和结肠癌。在许多情况下，这些疾病以及许多肠道感染反映了细菌与肠道上皮之间的致病相互作用。在体内研究这种微生物-上皮界面的复杂性导致了人们对使用类器官模型来模拟这种串扰的极大关注。考虑到类器官领域的发展速度如此之快，很难跟上最新技术的步伐，以及它们各自的优缺点。本文综述了使用源自成人干细胞的类器官的优势，以及活检部位和患者年龄对类器官及其与微生物相互作用的影响。还介绍了几种以相关（顶端）方式引入细菌的方法（即，三维球体微注射、极性反转类器官和二维单层），以及使用这些模型可以获得的关键读数。最后，评估了新方法（如气-液界面）的潜力，以促进研究细菌与重要但研究不足的上皮细胞亚群（如杯状细胞及其产物）的相互作用。
