ArticleJournal of gastroenterology2019
Establishment of a system to evaluate the therapeutic effect and the dynamics of an investigational drug on ulcerative colitis using human colonic organoids.
Article in Journal of gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Trans-ancestry, Bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian and European cohort.Human molecular genetics · 2023Pooled it
- Organoid Models of Colorectal Pathology: Do They Hold the Key to Personalized Medicine? A Systematic Review.Diseases of the colon and rectum · 2020Pooled it
- Article
- Review
- Harnessing 3D models to uncover the mechanisms driving infectious and inflammatory disease in the intestine.BMC biology · 2024Review
- Gastrointestinal tract organoids as novel tools in drug discovery.Frontiers in pharmacology · 2024Review
- Identification and immunoinfiltration analysis of key genes in ulcerative colitis using WGCNA.PeerJ · 2024Article
- Mechanism of Acupuncture and Moxibustion on Promoting Mucosal Healing in Ulcerative Colitis.Chinese journal of integrative medicine · 2023Review
- Organoids are not organs: Sources of variation and misinformation in organoid biology.Stem cell reports · 2023Review
- Comprehensive protocols for culturing and molecular biological analysis of IBD patient-derived colon epithelial organoids.Frontiers in immunology · 2023Article
- A multi-mineral intervention to counter pro-inflammatory activity and to improve the barrier in human colon organoids.Frontiers in cell and developmental biology · 2023Article
- Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer.Cancer discovery · 2022Article
- Interleukin-27 Regulates the Function of the Gastrointestinal Epithelial Barrier in a Human Tissue-Derived Organoid Model.Biology · 2022Article
- Enhancing responsiveness of human jejunal enteroids to host and microbial stimuli.The Journal of physiology · 2020Article
- Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases.World journal of gastroenterology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundUlcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. The goal of UC therapy is to target mucosal healing because immune-suppressive therapy for UC frequently results in relapse. However, few drugs directly target mucosal healing. We, therefore, aim to evaluate the therapeutic effect of an investigational drug on intestinal epithelial cells in an in vitro UC model using human colonic organoids.
methodsColonic organoids were isolated from human colon and cultured. A mixture of cytokines and bacterial components were used to mimic UC in humans. The effect of the investigational drug on colonic organoid was evaluated by microarray analysis and 3D immunofluorescence. The enrichment of stem cells was assessed with a colony formation assay.
resultsInflammatory stimulation resulted in a significant induction of inflammatory-related genes in colonic organoids whereas cell differentiation was suppressed. Treatment with the investigational drug KAG-308 showed reciprocal dynamics of gene expression to inflammatory stimulation, which resulted in not only the suppression of immune response but also the promotion of cellular differentiation towards secretory lineages. Moreover, SPDEF and Reg4 were identified as novel targets for the enrichment of intestinal epithelial stem cells and mucosal healing.
conclusionsThe establishment of in vitro UC model using human colonic organoid could reveal the effects and targets of investigational drugs in intestinal epithelial cells under inflammation conditions. Further maturation of this system might be more efficient to predict the effect on UC, as compared with the use of animal model, for the development of new drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.