The Role of Organoids as a Novel Platform for Modeling of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting immune-mediated disorder affecting the gut. It is common in Westernized regions and is increasing in incidence in developing countries. At a molecular level, intrinsic deficiencies in epithelial integrity, mucosal barrier function, and mechanisms of immune response and resolution contribute to the development of IBD. Traditionally two platforms have been utilized for disease modeling of IBD; in-vitro monolayer cell culture and in-vivo animal models. Both models have limitations, including cost, lack of representative cell types, lack of complexity of cellular interactions in a living organism, and xenogeneity. Organoids, three-dimensional cellular structures which recapitulate the basic architecture and functional processes of the organ of origin, hold potential as a third platform with which to investigate the pathogenesis and molecular defects which give rise to IBD. Organoids retain the genetic and transcriptomic profile of the tissue of origin over time and unlike monolayer cell culture can be induced to differentiate into most adult intestinal cell types. They may be used to model intestinal host-microbe interactions occurring at the mucosal barrier, are amenable to genetic manipulation and can be co-cultured with other cell lines of interest. Bioengineering approaches may be applied to render a more faithful representation of the intestinal epithelial niche. In this review, we outline the concept of intestinal organoids, discuss the advantages and disadvantages of the platform comparative to alternative models, and describe the translational applications of organoids in IBD.

Molecular and Functional Characterization of Human Intestinal Organoids and Monolayers for Modeling Epithelial Barrier

“…Previously, most epithelial research relied on cancer-derived nonprimary monocultures or nonhuman in vivo models, both of which lack the ability to accurately replicate the human intestinal niche. 4 Recent breakthroughs in culturing intestinal stem cells allowed the emergence of patient-derived organoids (PDOs) as a promising patient-relevant human primary cell model. 5 , 6 Patient-derived organoids are generated from crypt basal stem cells extracted from endoscopic biopsies or surgical resection material.…”

Interleukin-27 Regulates the Function of the Gastrointestinal Epithelial Barrier in a Human Tissue-Derived Organoid Model

“…Although useful for certain investigations, cell line models do not always reflect in function and can biologically change over time. The advent of organoid culture has revolutionised this field [29], offering advantages of near physiological modelling, reflection of patient heterogeneity and a mirror of molecular and morphological identity to source tissue [30][31][32]. There is emerging evidence for the utility of organoid methodology to gain novel insights into the pathogenesis of IBD [33][34][35][36] and for advocating the use of organoid technology to aid assessment of new IBD treatment targets [37,38].…”

Therapeutic Potential of Bioactive Components from Scutellaria baicalensis Georgi in Inflammatory Bowel Disease and Colorectal Cancer: A Review

“…Organoids are produced by pluripotent or adult stem cells. They are three-dimensional and can be differentiated into different cell types to perform related organ functions [59]. Organoids mimic the physiology of intestinal cells [60,61] and ecology of gut microbes [62,63].…”