Two years ago, I started my PhD in the Immunogenetics lab run by Sebo Withoff and Iris Jonkers at the Department of Genetics of the University Medical Center Groningen in the context of the NOW Gravitation program ‘Netherlands Organ-on-Chip Initiative’ (NOCI). In our group we work with organoids and organ-on-chip systems as models for the intestine and the liver. My project mainly focusses on the intestine-on-chip, which we use to study coeliac disease pathophysiology.

Coeliac disease, also known as gluten intolerance, is a multifactorial complex disease where gluten intake triggers inflammatory responses in the small intestines of genetically predisposed individuals, in ~1% of the Western population. Modelling the complexity of this coeliac disease, including genetic, environmental (e.g. gluten; the microbiome) and immunological susceptibility factors is very challenging. Most currently used model systems do not contain the genetic susceptibility nor the complexity of the disease, specifically the combination of tissues involved. To overcome these shortcomings, we (NOCI PhD’s Renée Moerkens and Joram Mooiweer) have established intestinal organoid and intestine-on-chip platforms using the commercially available Emulate system, based on induced pluripotent stem cells (iPSCs) or adult stem cells (ASCs) cells obtained from patients and control individuals [1, 2].

In my project I compare intestinal epithelial cells (IECs) either derived from iPSCs (iPSC-IECs) or from ASCs (ASC-IECs). While iPSC-IECs are more fetal and are not derived from the intestine itself, ASC-IECs are thought to preserve epigenetic signatures from their original environment [3]. Utilizing both iPSC-IECs and ASC-IECs from patients allows to explore the role of (epi)genetic factors in barrier functionality in the context of celiac disease. At the moment, I am differentiating iPSCs towards iPSC-IECs and optimizing the systems to grow both iPSC-IECs and ASC-IECs in similar culture conditions. Multiple mature intestinal cell-types can be found in our iPSC-IEC chips, which self-organize in fold-like structures, creating a tight barrier (Figure 1A) [1]. Simultaneously we are piloting with ASC-IECs on our chips to characterize the cell-types on these barriers (Figure 1B).