Intestinal Stem Cells Characterization

Study Overview
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Brief Summary
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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
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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.

Official Title
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Intestinal Stem Cells Characterization in Intestinal Organoid Culture From Inflammatory Bowel Disease and Intestinal Polyposis Patients

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Procedure: Endoscopic biopsies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient must have a coloscopy for intestinal pain - Exclusion Criteria: cancer -

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crohn disorder<br>arm composed by 30 patients with Crohn disorder | Procedure: Endoscopic biopsies<br>* intestinal biopsies<br>|
| Experimental: FAP (familial adenomatous polyposis )<br>arm composed by 30 patients with FAP disorder | Procedure: Endoscopic biopsies<br>* intestinal biopsies<br>|
| Experimental: ulcerative colitis<br>arm composed by 30 patients with ulcerative colitis | Procedure: Endoscopic biopsies<br>* intestinal biopsies<br>|
| Sham Comparator: witness<br>arm composed by 30 patients with no intestinal disorders | Procedure: Endoscopic biopsies<br>* intestinal biopsies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of organoids | number of organoids in culture wells during the follow-up | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean size of organoids | mean diameter of organoids in culture wells during the follow-up | 2 days | 
| percentage of different types of organoids | organoids are differentiated by the size of the epithelial cell border and by the presence or absence of buds | 2 days |