Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches

Abstract

The recent emergence of organoid technology has attracted great attention in gastroenterology because the gastrointestinal (GI) tract can be recapitulated in vitro using organoids, enabling disease modeling and mechanistic studies. However, to more precisely emulate the GI microenvironment in vivo, several neighboring cell types and types of microbiota need to be integrated into GI organoids. This article reviews the recent progress made in elucidating the crosstalk between GI organoids and components of their microenvironment. We outline the effects of stromal cells (such as fibroblasts, neural cells, immune cells, and vascular cells) on the gastric and intestinal epithelia of organoids. Because of the important roles that microbiota play in the physiology and function of the GI tract, we also highlight interactions between organoids and commensal, symbiotic, and pathogenic microorganisms and viruses. GI organoid models that contain niche components will provide new insight into gastroenterological pathophysiology and disease mechanisms.

Fig. 1. Image of GI epithelium and the surrounding tissues.

In GI tissues, there are numerous interactions between the epithelium and microbes or other cells, such as fibroblasts, vascular cells, immune cells and neural cells. Their communication has significant effects on the functions and homeostasis of the epithelium, indicating the necessity of including stromal cells and microbiota for producing functional 3D organoid models of the GI tract.

Fig. 2. Coculture models of GI organoids with stromal cells and microbiota.

The biological effects of various stromal cells and microbiota on GI organoids in coculture models are described.

Fig. 3. Bioengineered platforms for developing GI organoids assembled with other types of organoids.

Through bioengineering techniques such as 3D bioprinting and the use of microfluidics and biomaterials, a novel integrated GI system can be developed by connecting the various organoids that make up the digestive system or by coculturing with completely different types of organoids such as brain organoids. These innovative organoid systems enable the modeling of highly complex human physiology, such as reciprocal regulation between the GI tract and other major organs, and pathological phenomena associated with diseases.