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2013|14 Annual Report Fraunhofer IGB

FRAUNHOFER PROJECT GROUP “REGENERATIVE TECHNOLOGIES IN ONCOLOGY” The project group “Regenerative Technologies in Oncology” performs in close collaboration with the Institute for Tissue Engineering and Regenerative Medicine at the University Hospital Würzburg methods and procedures to develop thera- peutics for cancer. These therapeutics are placed along the value chain in an interdisciplinary and international team – as a Würzburg Fraunhofer interface between health research and medicine engineering – applying human vascularized 3D (tu- mor) tissue models in preclinical and clinical studies. In Germany, 450,000 people suffer and 216,000 people die from cancer each year. After cardiovascular diseases, cancer is the second leading cause of death. Cancer cells grow uncon- trollably and form their own nutrient-supplying blood vessels. Many tumor cells move through the blood or lymphatic sys- tem to distant organs and form metastases, which often lead to incurable cancer. An important goal of our work is to there- fore discover the mechanisms of cancer growth, metastasis, and their distribution in the human body. The scientific focus of our research is on the development of human 3D tissue equivalents on an acelluarized, vascularized intestinal scaffold: BioVaSc. By applying tissue engineering methods, we produce human 3D tumor tissue on the BioVaSc in combination with primary tumor cells and various tumor cell lines to get the mechanisms of new therapy strategies in a complex human pathological environment examined. The project group succeeded in establishing various tumor models in different complexities such as lung tumor models or models for colorectal carcinoma, for breast cancer, leuke- mia and for malign peripheral nerve sheath tumors (MPNST). Beyond the standard divisional rate and apoptosis of tumor cells, various molecular activations and inhibitions of signal cascades can now be measured after a treatment with agents. Based on these data, “in silico”-models are created, refined, and validated in cooperation with the Department of Bioinfor- matics of the University Hospital of Würzburg. The co-culture with cells from the tumor stroma additionally allows the examination of the reciprocity of agents, among them bio- logicals such as anti-bodies, with stromal and with tumor cells of their surroundings, and to further examine the formation of resistance or metastases. In the future, we want to refine characteristics of metastasizing tumor stem cells. The application of 2D monolayer cultures and cell lines is limited when clarifying certain regenerative mechanisms, the examination of physiological barrier functions, and the resorption processes in humans. Based on the BioVaSc, we developed complex tissue models of the human barriers skin, intestine, trachea, lung and the blood-brain-barrier. We adapt these tissues to diseases (disease-models) or we simulate in- fections of germs and, accordingly, we establish long-time cul- tures. Equally, we simulate reciprocal effects of medical prod- ucts such as stents to optimize the surface of the implants. In the EU project IDEA, we use vascularized tissue models to develop diagnostics (nanoparticles) and to test their safety. In the EU projects Bio-Inspire and VascuBone, we are developing stem cell-based musculoskeletal therapies; the necessary pre- clinical studies are in progress with international partners from COMPETENCES 62

Overview