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.
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
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
110
intestinal biopsies
Hopital des Enfants
Toulouse, France
number of organoids
number of organoids in culture wells during the follow-up
Time frame: 2 days
mean size of organoids
mean diameter of organoids in culture wells during the follow-up
Time frame: 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
Time frame: 2 days
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