Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Aug 14;25(30):4125-4147.
doi: 10.3748/wjg.v25.i30.4125.

Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases

Jun-Hwan Yoo  1 , Mark Donowitz  1
Affiliations
Review

Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases

Jun-Hwan Yoo et al. World J Gastroenterol. .

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

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest.

Figures

Figure 1
Figure 1
The normal intestinal epithelial barrier functions. A: Physical barrier function; B: Biochemical barrier function; C: Innate immune barrier function. TFFs: Trefoil factors; ISCs: Intestinal stem cells; TJ: Tight junction; AJ: Adherens junction; MUC2: Mucin2; BEST2: Bestrophin2; TFF3: Trefoil factor3; REGIIIγ: Regenerating islet-derived protein IIIγ; UPR: Unfolded protein response; TLR: Toll like receptor; NLR: Nod like receptor; NF-kB: Nuclear factor kappa B; Th: T helper; Treg: Regulatory T cells; gp180: Glycoprotein-180; CD: cluster of differentiation; TCR: T cell receptor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Okamoto R, Watanabe M. Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease. J Gastroenterol. 2016;51:11–21. - PubMed
    1. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474:307–317. - PMC - PubMed
    1. Frolkis AD, Dykeman J, Negrón ME, Debruyn J, Jette N, Fiest KM, Frolkis T, Barkema HW, Rioux KP, Panaccione R, Ghosh S, Wiebe S, Kaplan GG. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology. 2013;145:996–1006. - PubMed
    1. Ruffolo C, Scarpa M, Bassi N. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;363:1086–1087; author reply 1087-1088. - PubMed
    1. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA, Johanns J, Gao LL, Miao Y, Adedokun OJ, Sands BE, Hanauer SB, Vermeire S, Targan S, Ghosh S, de Villiers WJ, Colombel JF, Tulassay Z, Seidler U, Salzberg BA, Desreumaux P, Lee SD, Loftus EV, Jr, Dieleman LA, Katz S, Rutgeerts P UNITI–IM-UNITI Study Group. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016;375:1946–1960. - PubMed

MeSH terms

Substances