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Celiac disease-on-chip: Modeling a multifactorial disease in vitro. Conventional model systems cannot fully recapitulate the multifactorial character of complex diseases like celiac disease (CeD), a common chronic intestinal disorder in which many different genetic risk factors interact with environmental factors such as dietary gluten. However, by combining recently developed human induced pluripotent stem cell (hiPSC) technology and organ-on-chip technology, in vitro intestine-on-chip systems can now be developed that integrate the genetic background of complex diseases, the different interacting cell types involved in disease pathology, and the modulating environmental factors such as gluten and the gut microbiome. The hiPSCs that are the basis of these systems can be generated from both diseased and healthy individuals, which means they can be stratified based on their load of genetic risk factors. A CeD-on-chip model system has great potential to improve our understanding of disease etiology and accelerate the development of novel treatments and preventive therapies in CeD and other complex diseases.