Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases.
Biological Products
/ pharmacology
Biopsy
Drug Discovery
/ methods
Drug Evaluation, Preclinical
/ methods
Epithelial Cells
Humans
Immunosuppressive Agents
/ pharmacology
Induced Pluripotent Stem Cells
Inflammatory Bowel Diseases
/ drug therapy
Intestinal Mucosa
/ cytology
Organoids
/ drug effects
Primary Cell Culture
/ methods
Crohn’s disease
Enteroids
Inflammatory bowel diseases
Organoids
Ulcerative colitis
Journal
World journal of gastroenterology
ISSN: 2219-2840
Titre abrégé: World J Gastroenterol
Pays: United States
ID NLM: 100883448
Informations de publication
Date de publication:
14 Aug 2019
14 Aug 2019
Historique:
received:
27
03
2019
revised:
14
06
2019
accepted:
19
07
2019
entrez:
23
8
2019
pubmed:
23
8
2019
medline:
15
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31435168
doi: 10.3748/wjg.v25.i30.4125
pmc: PMC6700704
doi:
Substances chimiques
Biological Products
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4125-4147Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK089502
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK099803
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK085532
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK085532
Pays : United States
Déclaration de conflit d'intérêts
Conflict-of-interest statement: No potential conflicts of interest.
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