Inflammatory Bowel Diseases
Conditions
Keywords
Crohn's disease, ulcerative colitis, mesenchymal stem cells, intestinal inflammation
Brief summary
The exact origin of inflammatory bowel disease (IBD) is still unknown. The current hypothesis is that IBD is secondary to an abnormal intestinal immun response directed to all or part of the intestinal flora in genetically predisposed individuals. Several experimental studies have demonstrated the ability of mesenchymal stem cells (MSCs) from bone marrow or adipose tissue origin to control intestinal inflammation in animal models. However, to date, there are no data regarding the functions of resident MSCs in the colon and small intestine of IBD patients. We hypothesize that dysfunction of resident intestinal MSCs contributes to the disruption of intestinal homeostasis in patients with IBD causing the development of intestinal inflammation. The aim of this research project is to identify, describe and characterize at the molecular and functional level MSCs of the colon and small intestine of patients with Crohn's disease and ulcerative colitis and to compare them with a control population.
Detailed description
Primary and secondary objectives: Main Objective: Characterize morphologically, molecularly and functionally the MSCs of colon and small intestine of patients with IBD and compared to MSCs of colon and small intestine of control patients. Secondary objectives: To study the reaction of colon and small intestine MHC in patients with IBD following stimulation with bacterial compounds. Methodology: Clinical study exploratory translational physiopathological. Two groups of patients with Crohn's disease and ulcerative colitis who require colonoscopy or surgery for intestinal resection will be included. These two groups will be compared to a control group consisting of patients requiring colonoscopy for screening or intestinal resection for colorectal cancer or diverticulum. Intestinal sampling by biopsy during the colonoscopy or with surgical specimen during the surgery will be performed to isolate the MSCs. The outcome measures will be a qualitative and quantitative analysis of MSCs by immunohistochemistry, immunofluorescence, cell proliferation and differentiation, production of pro- and anti-inflammatory cytokines in the basal state and after bacterial stimulation. Total of 60 patients (20 in groups, 15 with colonoscopy and 5 with surgical specimens).
Interventions
OTHERIntestinal biopsies during colonoscopy
Intestinal biopsies during colonoscopy
OTHERBiopsies taken on surgical specimen
biopsies taken on surgical specimen after intestinal resection
Sponsors
University Hospital, Montpellier
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* For IBD patients : * Age between 18 and 75 year old * Diagnosis of Crohn's disease or ulcertaive colitis according to internationla guidelines * Endoscopically active disease * Indication for colonoscopy or intestinal resection according to standard of care * Written inform consent * For control patients : * Age between 18 and 75 year old * Indication for screening colonoscopy for irritable bowel syndrome, diverticulum or colorectal cancer surveillance according to standard of care * Indication for intestinal resection for diverticulum or colorectal cancer according to standard of care * Written inform consent
Exclusion criteria
* For IBD patients : * Active intestinal infection * Confirmed intestinal parasitosis * Intestinal stoma * For control patients : * Active intestinal infection * Confirmed intestinal parasitosis * Intestinal inflammation at colonoscopy * Chronic intestinal inflammation on biopsies * Absence of healthy tissue on surgical specimen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proliferation and differentiation of intestinal MSCs in IBD patients. | 1 month | Proliferation and differentiation of intestinal MSCs in IBD patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of MSCs between IBD patients and control patients | 1 month | Comparison of MSCs between IBD patients and control patients using mmunohistochemistry, immunofluorescence, quantification of pro- and anti-inflammatory cytokines production. |
Countries
France
Outcome results
None listed