Identification number: LZP-2023/1-0378
Type: Latvian Council of Science Fundamental and Applied Research project
Duration: 01.01.2024-31.12.2026
Project Leader: Dr. Caroline Kuestermann, Latvian Biomedical Research and Study Centre
Responsible person from Institute of Solid State Physics, University of Latvia (ISSP UL): Dr. Maira Elksne
Project partners: Latvian Biomedical Research and Study Centre
Total budget: 300 000 EUR
ISSP UL budget: 90 000 EUR
Project description:
Celiac Disease (CeD) is incurable autoimmune disorder that affects the small intestine and is caused by gluten, barley and rye ingestion. CeD has a strong genetic component as individuals carrying HLA-DQ2 or HLA-DQ8 variant have a higher risk of developing the disease. It is more common in individuals with familial history of the disease. When CeD patient consumes gluten, their immune system reacts by attacking the lining of the intestine, leading to inflammation and damage of the villi. Unfortunately, there are no human based in vitro models for CeD and only one mouse model available. Therefore, we aim to model the pathogenesis of CeD by using patient derived induced pluripotent stem cells (iPSC) in CeD on a PDMS-free organ chip (CDOC) through the following tasks: reprogramming patient and healthy donor somatic cells into iPSC, differentiate patient and healthy donor derived iPSC into intestinal organoids and endothelial cells and seed them on the chip in a co-culture with patient peripheral blood mononuclear cells and evaluate the villous structures during co-culture. After the model is established pathogenesis will be induced with gluten and disease model and healthy villi structures will be evaluated by immunofluorescence, gut barrier integrity measurements and cytokine secretion.
The establishment of CDOC will give a model for future development of drugs and treatment of CeD and a better understanding of the disease ethiology.