Intestinal Organoids – a Powerful Model to Study Interactions of the Epithelial Barrier with its Environment

Ulrika C. Frising, Jörg Stange,, Marc Veldhoen

Abstract


The gastrointestinal (GI) tract is the body’s largest mucosal area exposed to the external environment. It harbours a large and diverse community of commensal microorganisms. The GI tract is lined by a monolayer of epithelial cells that separates the intestinal lumen and underlying tissues. It is not only a physical barrier - it interacts with commensal microorganisms and immune cells by mechanisms that are not fully defined. The intestinal immune system must maintain the balance between offering adequate protection against pathogens, while remaining tolerant to harmless antigens from commensals and diet. Imbalances in these immune responses may lead to the development of chronic inflammatory disorders such as inflammatory bowel disease (IBD). Despite intense research, the molecular mechanisms governing intestinal homeostasis remain to be fully understood. To help defining these complex mechanisms, we adapted the small intestinal organoid model. We isolated small intestinal crypts according to the protocol recently published by Sato and Clevers, 2013. In the presence of the growth factors epidermal growth factor (EGF), Noggin and R-spondin-1 crypts, containing intestinal epithelial stem cells, form organoids. The organoids resemble the in vivo organisation of the epithelial barrier. Technologies like confocal microscopy and live cell imaging will enable us to follow changes in the intestinal epithelial cells (IECs) in detail and in real-time. We propose that analysis of intestinal organoids in the presence of immune cells and mediators, diet-derived molecules and / or commensal microorganisms will facilitate the discovery of molecular mechanisms directing intestinal homeostasis, thus making it a powerful model to study the interactions of the epithelial barrier with its environment.

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Copyright (c) 2014 Ulrika C. Frising, Jörg Stange,, Marc Veldhoen