Establishment of mini-guts organoid and research on intestinal disease from the new perspective

Abstract

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.