Intestinal Stem Cells Characterization (BIODIGE)

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Procedure: Endoscopic biopsies

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 Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31159
    • Hopital des Enfants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Exclusion Criteria: cancer

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Emmanuel MAS, MD, PhD, University Hospital, Toulouse

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 27, 2023

Study Registration Dates

• First Submitted: May 13, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimated): August 22, 2016

Study Record Updates

• Last Update Posted (Estimated): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Endoscopic Mucosal Resection
• Other Study ID Numbers: RC31/15/7816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO