BIODIGE: Intestinal Stem Cells Characterization
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Crohn disorder arm composed by 30 patients with Crohn disorder |
Procedure: Endoscopic biopsies
intestinal biopsies
|
| Experimental: FAP (familial adenomatous polyposis ) arm composed by 30 patients with FAP disorder |
Procedure: Endoscopic biopsies
intestinal biopsies
|
| Experimental: ulcerative colitis arm composed by 30 patients with ulcerative colitis |
Procedure: Endoscopic biopsies
intestinal biopsies
|
| Sham Comparator: witness arm composed by 30 patients with no intestinal disorders |
Procedure: Endoscopic biopsies
intestinal biopsies
|
Outcome Measures
Primary Outcome Measures
- number of organoids [2 days]
number of organoids in culture wells during the follow-up
Secondary Outcome Measures
- mean size of organoids [2 days]
mean diameter of organoids in culture wells during the follow-up
- percentage of different types of organoids [2 days]
organoids are differentiated by the size of the epithelial cell border and by the presence or absence of buds
Eligibility Criteria
Criteria
Inclusion Criteria: patient must have a coloscopy for intestinal pain -
Exclusion Criteria: cancer
-
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hopital des Enfants | Toulouse | France | 31159 |
Sponsors and Collaborators
- University Hospital, Toulouse
Investigators
- Principal Investigator: Emmanuel MAS, MD, PhD, University Hospital, Toulouse
Study Documents (Full-Text)
None provided.More Information
Publications
- RC31/15/7816