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World J Gastroenterol. Jun 28, 2022; 28(24): 2636-2653
Published online Jun 28, 2022. doi: 10.3748/wjg.v28.i24.2636
Patient-derived organoids for therapy personalization in inflammatory bowel diseases
Marianna Lucafò, Antonella Muzzo, Martina Marcuzzi, Lorenzo Giorio, Giuliana Decorti, Gabriele Stocco
Marianna Lucafò, Giuliana Decorti, Gabriele Stocco, Advanced Translational Diagnostics Laboratory, Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, Trieste 34137, Italy
Antonella Muzzo, Giuliana Decorti, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34127, Italy
Martina Marcuzzi, Lorenzo Giorio, Gabriele Stocco, Department of Life Sciences, University of Trieste, Trieste 34127, Italy
Author contributions: Lucafò M, Decorti G, and Stocco G contributed to the conceptualization; Lucafò M, Muzzo A, Marcuzzi M, and Giorio L wrote the original draft; Lucafò M, Decorti G, and Stocco G wrote the review and edited the review; all authors have read and agree to the published version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Giuliana Decorti, MD, Associated Professor, Advanced Translational Diagnostics Laboratory, Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, Via dell’Istria 65/1, Trieste 34137, Italy.
Received: January 17, 2022
Peer-review started: January 17, 2022
First decision: March 8, 2022
Revised: March 21, 2022
Accepted: May 17, 2022
Article in press: May 17, 2022
Published online: June 28, 2022

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract that have emerged as a growing problem in industrialized countries. Knowledge of IBD pathogenesis is still incomplete, and the most widely-accepted interpretation considers genetic factors, environmental stimuli, uncontrolled immune responses and altered intestinal microbiota composition as determinants of IBD, leading to dysfunction of the intestinal epithelial functions. In vitro models commonly used to study the intestinal barrier do not fully reflect the proper intestinal architecture. An important innovation is represented by organoids, 3D in vitro cell structures derived from stem cells that can self-organize into functional organ-specific structures. Organoids may be generated from induced pluripotent stem cells or adult intestinal stem cells of IBD patients and therefore retain their genetic and transcriptomic profile. These models are powerful pharmacological tools to better understand IBD pathogenesis, to study the mechanisms of action on the epithelial barrier of drugs already used in the treatment of IBD, and to evaluate novel target-directed molecules which could improve therapeutic strategies. The aim of this review is to illustrate the potential use of organoids for therapy personalization by focusing on the most significant advances in IBD research achieved through the use of adult stem cells-derived intestinal organoids.

Keywords: Inflammatory bowel disease, Organoids, Intestinal epithelium, 3D cell cultures, Personalized medicine

Core Tip: Intestinal organoids have helped to unveil knowledge about inflammatory bowel diseases pathogenesis, focusing on the genetic and epigenetic factors involved in the onset of these diseases, the altered intestinal epithelial cell (IEC) functions, and the interplay between IECs and other surrounding cells, including immune cells and the intestinal bacteria. Intestinal organoids are currently being evaluated in pre-clinical studies as pharmacological tools to better understand the specific mechanisms of action of already used drugs on the IECs and to identify novel pharmacological targets and approaches.