Intestinal Stem Cells Characterization (BIODIGE)

Toulouse University Hospital

Status: Completed

Conditions: Inflammatory Bowel Diseases

Treatments: Procedure: Endoscopic biopsies

Study type: Interventional

Funder types: Other

Identifiers

NCT02874365

RC31/15/7816

Details and patient eligibility

About

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.

Full 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.

Enrollment: 110 patients

Sex: All

Ages: 3+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Exclusion Criteria: cancer

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 4 patient groups

Crohn disorder

Experimental group

Description:

arm composed by 30 patients with Crohn disorder

Treatment:

Procedure: Endoscopic biopsies

FAP (familial adenomatous polyposis )

Experimental group

Description:

arm composed by 30 patients with FAP disorder

Treatment:

Procedure: Endoscopic biopsies

ulcerative colitis

Experimental group

Description:

arm composed by 30 patients with ulcerative colitis

Treatment:

Procedure: Endoscopic biopsies

witness

Sham Comparator group

Description:

arm composed by 30 patients with no intestinal disorders

Treatment:

Procedure: Endoscopic biopsies