Project title: Modelling celiac disease on-a-chip
Project No.: lzp-2023/1-0378
Period: 1 January 2024 – 31 December 2026
Project costs: 300 000,00 EUR
Principal Investigator: PhD Caroline Kuestermann
Cooperation partner: Institute of Solid State Physics, University of Latvia
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 carring 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 pathogensis 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 villious stuctures 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 measurments 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.
Information published 02.01.2024.