Clinical trial NCT02874365: Intestinal Stem Cells Characterization
Official title: Intestinal Stem Cells Characterization in Intestinal Organoid Culture from Inflammatory Bowel Disease and Intestinal Polyposis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammatory Bowel Diseases
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2016-08-22
Enrollment: 110
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: A monocentric pilot studying intestinal organoids from endoscopic biopsies of IBD (Crohn and ulcerative colitis), FAP patients and healthy controls. Investigate the morphological characteristics of organoids, the expression of genes and proteins of the Wnt/APC/beta-catenin pathway within both ISC.

Detailed description: Intestinal organoids are 3D mini-guts produced in vitro based on intestinal stem cell (ISC) capabilities. These organoids contain all of the intestinal epithelial cells. The renewal of the two kinds of ISCs, which are present at the bottom of intestinal crypts, is controlled by Wnt/APC/beta-catenin pathway. Mutations of genes involved in this pathway are found in intestinal polyposes like familial adenomatous polyposis (FAP, APC gene).

This model is of interest to study early pathophysiological events occurring within intestinal epithelium, in the context of FAP and inflammatory bowel diseases (IBD). An excessive proliferation or an abnormal healing is found in FAP and IBD respectively. Investigators hypothesized that it could specifically involved one of the 2 ISCs. Columnar basal cells (CBC) and ISC located at the +4 position from the bottom of the crypt (ISC+4) can both differentiate into absorptive or secretory intestinal epithelial cells. However, CBC and ISC+4 could have different metabolic, migratory functions, or stress survival.

Investigators designed a monocentric pilot study to develop intestinal organoids from endoscopic biopsies of IBD (Crohn and ulcerative colitis), FAP patients and healthy controls. Investigators plan to investigate the morphological characteristics of organoids, the expression of genes and proteins of the Wnt/APC/beta-catenin pathway within both ISC. Will also be studied the expression of key genes of tumor initiation (PTEN, BMPR1A, p53 and KRAS) and inflammatory parameters (cytokines and lipid mediators).

The results of this study could improve the understanding of intestine renewal. Later on, the development of new drugs could beneficiate to IBD and FAP patients.

Eligibility criteria: Inclusion Criteria: patient must have a coloscopy for intestinal pain -

Exclusion Criteria: cancer

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Primary outcomes:
measure: number of organoids
timeFrame: 2 days
Secondary outcomes:
measure: mean size of organoids
timeFrame: 2 days
measure: percentage of different types of organoids
timeFrame: 2 days
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Hopital des Enfants
Study officials:
affiliation: University Hospital, Toulouse
name: Emmanuel MAS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Laborde N, Barusseaud A, Quaranta M, Rolland C, Arrouy A, Bonnet D, Kirzin S, Sola-Tapias N, Hamel D, Barange K, Duffas JP, Gratacap MP, Guillermet-Guibert J, Breton A, Vergnolle N, Alric L, Ferrand A, Barreau F, Racaud-Sultan C, Mas E. Human colonic organoids for understanding early events of familial adenomatous polyposis pathogenesis. J Pathol. 2025 Jan;265(1):26-40. doi: 10.1002/path.6366. Epub 2024 Dec 6.
citation: Moreau J, Mas E. Drug resistance in inflammatory bowel diseases. Curr Opin Pharmacol. 2015 Dec;25:56-61. doi: 10.1016/j.coph.2015.11.003. Epub 2015 Nov 29.