Farm Animal-derived Models of the Intestinal Epithelium: Recent Advances and Future Applications of Intestinal Organoids

Abstract

Farm animals play an important role in translational research as large animal models of the gastrointestinal (GI) tract. The mechanistic investigation of zoonotic diseases of the GI tract, in which animals can act as asymptomatic carriers, could provide important information for therapeutic approaches. In veterinary medicine, farm animals are no less relevant, as they can serve as models for the development of diagnostic and therapeutic approaches of GI diseases in the target species. However, farm animal-derived cell lines of the intestinal epithelium are rarely available from standardised cell banks and, in addition, are not usually specific for certain sections of the intestine. Immortalised porcine or bovine enterocytic cell lines are more widely available, compared to goat or sheep-derived cell lines; no continuous cell lines are available from the chicken. Other epithelial cell types with intestinal section-specific distribution and function, such as goblet cells, enteroendocrine cells, Paneth cells and intestinal stem cells, are not represented in those cell line-based models. Therefore, intestinal organoid models of farm animal species, which are already widely used for mice and humans, are gaining importance. Crypt-derived or pluripotent stem cell-derived intestinal organoid models offer the possibility to investigate the mechanisms of inter-cell or host-pathogen interactions and to answer species-specific questions. This review is intended to give an overview of cell culture models of the intestinal epithelium of farm animals, discussing species-specific differences, culture techniques and some possible applications for intestinal organoid models. It also highlights the need for species-specific pluripotent stem cell-derived or crypt-derived intestinal organoid models for promotion of the Three Rs principles (replacement, reduction and refinement).

Keywords: crypt-derived; development; differentiation; farm animals; infection; intestinal organoids; intestinal stem cells; pluripotent stem cells; translational research; veterinary medicine.