Organoid Models of Human Gastrointestinal Development and Disease

Abstract

We have greatly advanced our ability to grow a diverse range of tissue-derived and pluripotent stem cell-derived gastrointestinal (GI) tissues in vitro. These systems, broadly referred to as organoids, have allowed the field to move away from the often nonphysiological, transformed cell lines that have been used for decades in GI research. Organoids are derived from primary tissues and have the capacity for long-term growth. They contain varying levels of cellular complexity and physiological similarity to native organ systems. We review the latest discoveries from studies of tissue-derived and pluripotent stem cell-derived intestinal, gastric, esophageal, liver, and pancreatic organoids. These studies have provided important insights into GI development, tissue homeostasis, and disease and might be used to develop personalized medicines.

Keywords: Gastrointestinal Development; Gastrointestinal Disease; Gastrointestinal Regeneration; Gut Organoids.

Figure 1. Composition, Cellular Sources and Nomenclature for GI Organotypic Culture Systems

GI organotypic cultures consist of short-term explant cultures and long-term organoid cultures. The 3 types of GI organoid cultures include 1) tissue-derived epithelial, 2) tissue-derived epithelial–mesenchymal, and 3) PSC-derived organoids. Tissue-derived epithelium and PSC-derived intestinal organoids are shown as examples of each type of tissue.

Figure 2. GI organ diversity represented in organoid systems

GI organoids have been generated from esophagus, liver, biliary tree, stomach, pancreas, small intestine, and large intestine. (Note: GI tract schematic modified from reference 4).