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.

Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability

“…A number of studies in the past decade have raised concerns about the reliability of methods used to model and test intestinal mucosa [22,28,29,31,53]. One of the most common strategies is the in vitro use of intestinal cell lines, but this approach has been shown to have signi cant drawbacks, including technical limitations and di culty in correlating results with in vivo data obtained from animal models [22,31].…”

Loss of RpoS results in attenuatedEscherichia colicolonization of human intestinal organoids and a competitive disadvantage within the germ-free mouse intestine

“…To this end, Sidar et al recently developed a multifluidic device that "ports" HIOs to establish steady-state liquid flow through the lumen for several days, thus eliminating luminal waste while maintaining the structural integrity of 3-D organoids (38). These examples illustrate how HIOs can be manipulated to better recapitulate in vivo intestinal structure and physiology, thus creating novel tools for investigating mechanisms modulating epithelial-microbe interactions within the gut (12). In this regard, our ∆rpoS E. coli mutant, or other bacterial "probes," can serve as a means of comparing these emerging systems and provide insight into how closely they mirror the in vivo gut environment from a microbial perspective.…”

“…However, technological advancements have expanded the repertoire of systems available for studying host-microbe interactions at the intestinal interface. In this regard, stem-cell-derived human intestinal organoids (HIOs) have emerged as powerful tools to investigate epithelial structure and function following initial interactions with a range of bacterial species (11)(12)(13).…”

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

“…Moreover, the lining of the gastrointestinal tract is subjected to the external environment and requires immune function, which is achieved by the intestinal mucus layer. In order to study the immune interactions in the gut, various culture models have been used, ranging from a 2D Caco-2 cell layer interacting with THP-1 monocytes [ 92 ] to intestinal organoids with microbiota niches [ 93 ]. Ideally, intestinal models should include an epithelial layer, immune component, peristaltic motion, microbial interactions, mucus and transport of nutrients [ 16 ].…”