Human intestinal organoids: Modeling gastrointestinal physiology and immunopathology — current applications and limitations

Abstract

Human intestinal organoids are an ideal model system to study gastrointestinal physiology and immunopathology. Altered physiology and mucosal immune response are hallmarks of numerous intestinal functional and inflammatory diseases, including inflammatory bowel disease (IBD), coeliac disease, irritable bowel syndrome (IBS), and obesity. These conditions impact the normal epithelial functions of the intestine, such as absorption, barrier function, secretion, and host‐microbiome communication. They are accompanied by characteristic intestinal symptoms and have significant societal, economic, and healthcare burdens. To develop new treatment options, cutting‐edge research is required to investigate their aetiology and pathology. Human intestinal organoids derived from patient tissue recapitulate the key physiological and immunopathological aspects of these conditions, providing a promising platform for elucidating disease mechanisms. This review will summarise recent reports on patient derived human small intestinal and colonic organoids and highlight how these models have been used to study intestinal epithelial functions in the context of inflammation, altered physiology and immune response. Furthermore, it will elaborate on the various organoid systems in use and the techniques/assays currently available to study epithelial functions. Finally, it will conclude by discussing the limitations and future perspectives of organoid technology.This article is protected by copyright. All rights reserved

Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids

“…Many genetic analyses have revealed that these "tumoroids" highly conserve their genomic landscape, making them a suitable source to investigate genotype-phenotype correlations and perform drug screening, confirming the importance of organoids in terms of biobanking and the subsequent development of precision medicine [35]. Gut organoid models are among the most developed and have been intensively described in recent reviews [36][37][38][39]. Colon organoids represent useful applications for the identification of potential drug targets in the treatment of genetic disorders.…”

The application of organoids in colorectal diseases

“…The differentiation medium is based on the expansion medium but lacks components such as Wnt family member 3A (WNT3A). It is used to induce the transformation of stem cells into diverse terminally differentiated colonic epithelial cell lineages ( Flood et al, 2023 ).…”

Development of an intestinal epithelial cell line and organoids derived from the same swine and characterization of their antiviral responses

“…Considering that the intestinal tract is composed of various cell types, including absorptive epithelial cells, goblet cells, Paneth cells, enteroendocrine cells, BEST4 cells, and intestinal stem cells [12,13], it may be difficult to accurately reproduce the response and function of the intestinal tract when relying solely on cell lines composed of a single cell type. Intestinal organoids, which can self-organize in three dimensions and reproduce the heterogeneity and behavior of the intestinal mucosa, are attractive tools to study in vitro the complex interactions between the different cell types and foreign agents, such as commensal or pathogenic microorganisms [14,15]. Several swine intestinal organoids have been constructed, which has allowed functional evaluations and viral infection studies [16][17][18], bridging the gap between in vitro and in vivo studies in pigs.…”