Xu Z Y, Liu Y, Jiang Y G, Huang J J, Wu X W, Ren J A
Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Jul 25;24(7):638-643. doi: 10.3760/cma.j.cn.441530-20200422-00236.
Intestinal organoids, also named "mini-guts", reconstitute sophisticated three-dimensional architecture recapitulating diversified intestinal epithelial cell types and physiology, which is driven by the proliferative and self-assembling characteristics of crypt stem cells. The initiation of organoids study relies on the identification of Lgr5+ crypt stem cells from different intestinal segments and the key role of EGF, Wnt, BMP/TGF-β, Notch signal pathways within the microenvironment during the cultivation process. Besides constituting polarized crypt-villus structures, these "mini-guts" exhibit various effective functions of intestinal epithelium. Since 2009 when the culture system of small intestinal organoids was established by Sato et al, intestinal organoids excel conventional intestinal models depending on genetical mutation in multiple aspects and thus have become the hotspot among the research on intestinal diseases. Combined with genomics, material science and engineering, "mini-guts" have been widely applied to the research on intestinal development, intestinal transport physiology, epithelial barrier, pathogen-host interaction and the study on cystic fibrosis, infectious diarrhea, ulcerative colitis, Crohn's disease, intestinal cancer, etc. In this review, we summarize the new insights introduced by organoid into the research on intestinal diseases, and related research advances and applications.
肠道类器官，也被称为“迷你肠道”，能够重构复杂的三维结构，再现多样化的肠道上皮细胞类型和生理功能，这是由隐窝干细胞的增殖和自我组装特性驱动的。类器官研究的起始依赖于从不同肠道段鉴定出Lgr5 +隐窝干细胞，以及培养过程中微环境内表皮生长因子（EGF）、Wnt、骨形态发生蛋白（BMP）/转化生长因子-β（TGF-β）、Notch信号通路的关键作用。除了构成极化的隐窝 - 绒毛结构外，这些“迷你肠道”还展现出肠道上皮的各种有效功能。自2009年佐藤等人建立小肠类器官培养系统以来，肠道类器官在多个方面优于传统肠道模型，这取决于基因突变，因此已成为肠道疾病研究的热点。结合基因组学、材料科学和工程学，“迷你肠道”已广泛应用于肠道发育、肠道转运生理学、上皮屏障、病原体 - 宿主相互作用以及囊性纤维化、感染性腹泻、溃疡性结肠炎、克罗恩病、肠道癌等疾病的研究。在本综述中，我们总结了类器官为肠道疾病研究带来的新见解以及相关研究进展和应用。
