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ePaper created 2016-03-17, 15:06:18 | version 1.45.01
76 1 2 HUMAN 3D IN VITRO TEST SYSTEMS FOR INFECTION STUDIES Florian Groeber, Marco Metzger, Heike Walles, Maria Steinke Initial situation Humans are the only natural hosts for numerous pathogens. Because of this fact a large amount of data obtained from animal tests does not correlate with the infection mechanisms in the human organism. Thus, many aspects of correspond- ing diseases are still speculative and the development of new therapy processes and vaccines is possible only under complicated conditions. In order to research the interactions between human obligate pathogens and the host tissue, corresponding 3D in vitro tissue models similar to the physi- ologic circumstances of the human body are necessary. In the Translational Center “Regenerative Therapies for Oncology and Musculoskeletal Diseases”, the Würzburg branch of Fraunhofer IGB, the manufacture of 3D in vitro test systems is based on the BioVaSc-TERM® , a biological scaffold gained from pig gut. 3D in vitro test system for infection studies with Bordetella pertussis The bacterium Bordetella pertussis that elicits whooping cough attacks the human airways and is primarily located at the cilia of the airway mucosa. We successfully generated a 3D in vitro test system of the human airway mucosa with a high in vitro/in vivo correlation, equipped with functional cilia ig fter an infection with sterile-filtered culture supernatant of Bordetella pertussis, we note for example the complete destruction of airway epithelial cells, which consid- erably affects the protective function of the airway mucosa. 3D in vitro test system for the examination of human sleeping sickness Human sleeping sickness is a dangerous tropical disease caused by the eukaryotic pathogen Trypanosoma brucei and transmitted via the tsetse fly s soon as the pathogen spreads in the body, the treatment of this disease becomes very difficult Therefore, novel therapies aim to fight the pathogen already in the skin. In order to recapitulate this step, we used in vitro skin models with a high similarity to human skin that can be used as an alternative method to animal testing. In the first step, the natural infection path through the tse tse fly was established in vitro demonstrating that the fly accepts the skin model as a host (Fig. 2). Moreover, we were able to show that the sting leads to the transmission of trypano- somes. The trypanosomes were active inside the model for a long period, which verified the applicability of the in vitro skin models for infection studies with Trypanosoma brucei. Infection studies of intestine test systems with Salmonella and Campylobacter Human intestine pathogens such as Salmonella typhi and Campylobacter jejuni are the reason for numerous, serious gastrointestinal diseases. Existing bowel tissue models were further developed in the Translational Center by means of the BioVaSc-TERM® technology and the dynamic tissue culture. Thus, a more physiological enzyme and transport activity as well as cell morphology were shown. On this basis and in cooperation with the Institute for Molecular Infection Biology Würzburg (IMIB, Prof. Dr. Jörg Vogel’s workgroup), a human triple culture model was established which depicts the human PHARMACY epithelium connective tissue 12