Options
2007
Conference Paper
Titel
Development of a physiological three-dimensional intestinal test system
Titel Supplements
Abstract
Abstract
Background: The small intestine is where the majority of digestion takes place. Orally applied substances are taken up over the intestine epithelium into the blood vessel system. The evaluation of different substances regarding their toxicity is mainly still made by the LD50 via the use of animal experiments. Our aim is their limitation by the development of a 3D physiological intestinal test system. Methods: The matrix used in our intestine module consists of a porcine jejunal segment containing a vascular system. The vascular system is reseeded with primary microvascular endothelial cells and the lumen of the matrix with primary enterocytes or cells with similar characteristics (e.g. Caco-2 cells). The intestine model is cultivated in a bioreactor system under arterial perfusion with growth medium simulating physiological conditions. The absorption of different substances into the blood vessel system can be experimentally determined through the venous delivery. Characterisation and the proof of epithelial and endothelial cell monolayers take place by histological and immunohistological analysis. The evaluation of the epithelial barrier function and other qualification parameters are to be established in the future by the use of different substances via HPLC, ELISA and photometric methods. Results: In preliminary tests Caco-2 cells and endothelial cells could be successfully cocultivated during a 14-day period on the matrix. First absorption studies of peptides on a native small intestine segment were compared to our system. Perspectives: Our aim is the establishment of a physiological 3D intestinal in vitro test system. By the complexity of our test system an adjustment to the human body over pharmacokinetic models is quite conceivable. Oral bioavailability of drugs and active ingredients could be simply tested due to the given blood vessel structures in our test system.