Gut organoids: mini-tissues in culture to study intestinal physiology and disease

Am J Physiol Cell Physiol. 2019 Sep 1;317(3):C405-C419. doi: 10.1152/ajpcell.00300.2017. Epub 2019 Jun 19.

Abstract

In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. Recently, the development of three-dimensional cultures known as organoids has permitted the growth of normal crypt-villus units that recapitulate many aspects of intestinal physiology. Organoid culturing has also been applied to study gastrointestinal diseases, intestinal-microbe interactions, and colorectal cancer. These models are amenable to CRISPR gene editing and drug treatments, including high-throughput small-molecule testing. Three-dimensional intestinal cultures have been transplanted into mice to develop versatile in vivo models of intestinal disease, particularly cancer. Limitations of currently available organoid models include cost and challenges in modeling nonepithelial intestinal cells, such as immune cells and the microbiota. Here, we describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer.

Keywords: colon cancer; genetic editing; gut physiology; intestinal organoids; organoid culture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cells, Cultured
  • Gastrointestinal Diseases / pathology*
  • Gastrointestinal Diseases / physiopathology
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / physiopathology
  • Gastrointestinal Tract / pathology*
  • Gastrointestinal Tract / physiology*
  • Gastrointestinal Tract / physiopathology
  • Humans
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology
  • Intestinal Mucosa / physiopathology
  • Organoids / pathology*
  • Organoids / physiology*
  • Organoids / physiopathology