Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2019; 25(30): 4125-4147
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4125
Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases
Jun-Hwan Yoo, Mark Donowitz
Jun-Hwan Yoo, Mark Donowitz, Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
Jun-Hwan Yoo, Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam 13496, South Korea
Author contributions: Yoo JH and Donowitz M have substantial contributions to conception and design of the review, and literature review; Yoo JH drafted and edited the article; Donowitz M revised the manuscript critically for important intellectual content; Yoo JH and Donowitz M worked together for the final approval of the version to be published.
Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, No. 2015R1C1A1A02037048; and National Research Foundation of Korea funded by the Ministry of Science and ICT, No. 2019R1H1A1035601.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jun-Hwan Yoo, MD, PhD, Assistant Professor, Digestive Disease Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, South Korea. jhyoo@cha.ac.kr
Telephone: +82-31-8817180 Fax: +82-31-7805219
Received: March 27, 2019
Peer-review started: March 28, 2019
First decision: May 30, 2019
Revised: June 14, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 14, 2019
Processing time: 140 Days and 18 Hours
Abstract

The introduction of biologics such as anti-tumor necrosis factor (TNF) monoclonal antibodies followed by anti-integrins has dramatically changed the therapeutic paradigm of inflammatory bowel diseases (IBD). Furthermore, a newly developed anti-p40 subunit of interleukin (IL)-12 and IL-23 (ustekinumab) has been recently approved in the United States for patients with moderate to severe Crohn’s disease who have failed treatment with anti-TNFs. However, these immunosuppressive therapeutics which focus on anti-inflammatory mechanisms or immune cells still fail to achieve long-term remission in a significant percentage of patients. This strongly underlines the need to identify novel treatment targets beyond immune suppression to treat IBD. Recent studies have revealed the critical role of intestinal epithelial cells (IECs) in the pathogenesis of IBD. Physical, biochemical and immunologic driven barrier dysfunctions of epithelial cells contribute to the development of IBD. In addition, the recent establishment of adult stem cell-derived intestinal enteroid/organoid culture technology has allowed an exciting opportunity to study human IECs comprising all normal epithelial cells. This long-term epithelial culture model can be generated from endoscopic biopsies or surgical resections and recapitulates the tissue of origin, representing a promising platform for novel drug discovery in IBD. This review describes the advantages of intestinal enteroids/organoids as a research tool for intestinal diseases, introduces studies with these models in IBD, and gives a description of the current status of therapeutic approaches in IBD. Finally, we provide an overview of the current endeavors to identify a novel drug target for IBD therapy based on studies with human enteroids/organoids and describe the challenges in using enteroids/organoids as an IBD model.

Keywords: Enteroids; Organoids; Inflammatory bowel diseases; Crohn’s disease; Ulcerative colitis

Core tip: Although intestinal epithelial cells are regarded as crucial regulators of barrier function in the pathogenesis of inflammatory bowel diseases (IBD), the development of novel IBD drugs targeting intestinal barrier dysfunction has been hampered by the lack of long-term human intestinal epithelial cultures. Novel intestinal enteroids/organoids derived from adult intestinal stem cells, are expected to play an important role in developing novel drugs for diverse intestinal diseases. The main purpose of this review is to provide the current status of therapeutic approaches in IBD and to highlight the potential to use human enteroids/organoids as a platform to develop novel drugs for IBD.