Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4125
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
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.
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.