Organoids and Their Use in Modeling Gut Epithelial Cell Lineage Differentiation and Barrier Properties During Intestinal Diseases

Abstract

Maintenance of intestinal epithelium homeostasis is a complex process because of the multicellular and molecular composition of the gastrointestinal wall and the involvement of surrounding interactive signals. The complex nature of this intestinal barrier system poses challenges in the detailed mechanistic understanding of intestinal morphogenesis and the onset of several gut pathologies, including intestinal inflammatory disorders, food allergies, and cancer. For several years, the gut scientific community has explored different alternatives in research involving animals and in vitro models consisting of cultured monolayers derived from the immortalized or cancerous origin cell lines. The recent ability to recapitulate intestinal epithelial dynamics from mini-gut cultures has proven to be a promising step in the field of scientific research and biomedicine. The organoids can be grown as two- or three-dimensional structures, and are derived from adult or pluripotent stem cells that ultimately establish an intestinal epithelium that is composed of all differentiated cell types present in the normal epithelium. In this review, we summarize the different origins and recent use of organoids in modeling intestinal epithelial differentiation and barrier properties.

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“…Organoids have been an invaluable resource for the modeling and investigation of the human intestinal system (Corro et al., 2020). A key aspect of the native intestinal system is the barrier function of the intestinal epithelium, which safeguards against microorganisms and infectious agents while managing nutrient, water, and small molecule absorption and transport (Gomez & Boudreau, 2021). Therefore, creating a physiologically relevant human intestine model necessitates accurate representation of barrier function and nutrient absorption.…”

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“… 59,67 The advantage of these cells is that they can be extracted from different intestine sections and grown into polarized and differentiated epithelial cell lineages. 68 Intestinal organoids can also be acquired from pluripotent stem cells, by either reprogramming adult stem cells of various organs or from embryonic stem cells, 37,68 thus circumventing the invasive deep-body biopsies. In addition to epithelium, various cell models are available for endothelial cells such as human umbilical vein endothelial cells (HUVECs) or human intestinal microvascular endothelial cells (HIMECs), and for immune cells such as human peripheral blood mononuclear cells (PBMCs).…”