Dynamic intestinal tissue model to evaluate the absorption behaviour of different substances

Background: The 3R principle, first described by Russel and Burch in 1959, defines reduction, refinement and if possible the complete replacement of animal experiments. Animal experiments are ethically critical and their results cannot always be readily transferred to humans. For this reason more in vitro test systems must be developed, which must closely reflect cellular processes in the human organism. By the use of a natural collagen scaffold and a dynamic bioreactor system an improved physiological intestinal test system was developed at the Fraunhofer IGB in Stuttgart. Methods: Caco-2 cells and primary micro-vascular endothelial cells were co-cultivated in a 2-chamber bioreactor. The endothelial barrier simulates the in vivo gut-blood barrier for the systemic uptake of substances in the body. Contrary to static diffusion cells (e.g. Franz chamber), the bioreactor provides an apical and basolateral flow of culture media. Results: Under dynamic culture conditions the Caco-2 cells grow in a high prismatic manner, similar to enterocytes in vivo. The 3D dynamic co-culture model could be validated so far with substances that simulate high permeable, low permeable and efflux transport. Perspectives: Our test system should provide a basis for ADMET studies and the characterisation of different substances. The results should be validated for the prediction of systemic effects and for in vivo classification. Furthermore the cell line Caco-2 should be exchanged with primary enterocytes.