Celiac disease-on-chip: Modeling a multifactorial disease in vitro

Area of Science:

• Biomedical Engineering
• Gastroenterology
• Stem Cell Biology

Background:

• Complex diseases like celiac disease (CeD) involve multifactorial genetic and environmental interactions not fully captured by conventional models.
• Dietary gluten and the gut microbiome are key environmental factors in CeD pathogenesis.
• Human induced pluripotent stem cell (hiPSC) and organ-on-chip technologies offer new avenues for disease modeling.

Purpose of the Study:

• To develop an in vitro intestine-on-chip model system that integrates genetic and environmental factors relevant to celiac disease.
• To create a platform for studying the complex interplay of genetic predisposition, cellular pathology, and environmental triggers in CeD.
• To leverage hiPSC technology for patient-specific disease modeling.

Main Methods:

• Generation of hiPSCs from both celiac disease patients and healthy individuals, allowing stratification by genetic risk.
• Integration of hiPSC-derived intestinal cells and other relevant cell types into an organ-on-chip microfluidic device.
• Incorporation of environmental factors, including gluten exposure and simulated gut microbiome conditions, into the chip system.

Main Results:

• The developed intestine-on-chip system successfully recapitulates key aspects of celiac disease pathology.
• The model allows for the investigation of how genetic risk factors interact with environmental triggers like gluten.
• Stratification of hiPSCs enables the study of disease variability based on individual genetic backgrounds.

Conclusions:

• Intestine-on-chip systems integrating hiPSC technology represent a powerful tool for modeling complex diseases like celiac disease.
• This approach enhances understanding of disease etiology by simulating multifactorial interactions.
• The CeD-on-chip model holds significant potential for accelerating the development of targeted therapies and preventive strategies.