With a view to replacing dysfunctional organs and tissues or to restoring their function, the research focus in Area B (Reconstructive Therapy in Preclinical Models) is on cell therapy and tissue engineering. One of the aims is to develop a biohybrid lung replacement system able to fully assume the function of the damaged organ. The initial approach adopted involves seeking to extend the working life of the lung replacement systems already available. This involves repopulating the blood-contacting components with cells from the blood vascular system (endothelial cells).
One breakthrough in this research is the development of new methods for reprogramming somatic (body) cells to iPS cells. These iPS cells can be multiplied almost indefinitely in the lab and differentiated into many cell types – characteristics that have thus far been observed only in embryonic stem cells. Unlike the latter, harvesting of iPS cells does not raise any ethical questions, and it provides an opportunity, for the first time, to perform cell therapy that makes use of the body’s own stem cells without the risk of rejection. iPS cells do at present, however, still harbour certain risks – owing to the methods by which they are produced – which prevent their clinical application. High hopes are therefore currently being placed on the development of improved production methods that will make it possible to use iPS cells therapeutically for treating a very wide range of diseases and disorders in the future.
Another focus of the experimental investigations is the hepatic differentiation of embryonic stem cells or iPS cells and repopulation with stem cell-derived hepatocytes in standardized mouse models. The development of clinically relevant techniques for liver repopulation to improve cell therapy used in treating metabolic liver disorders is also important. Biothermodynamic processes that underlie the cryoconservation of biological samples are also analysed. Cryoconservation strategies for stem cells, tissue and products from tissue engineering are to be developed. The influence of biological temperature transport mechanisms on cell-cell interaction is also being investigated, as are signal transmission and changes in proteins and membranes. Moreover, different laser systems and imaging techniques for assessing and manipulating various cell systems are being researched in the context of regenerative medicine (biophotonics). In Area B, ultra-short pulse laser systems are also being used for innovative aspects of nanotechnology (such as surfaces, particles and scaffolds).
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Report for the Biological Section (C. Baum)
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REBIRTH’s Research Area B focuses on ‘Reconstructive therapy in preclinical models’. It was created to integrate developments arising from fundamental research into regenerative mechanisms (Area A) and the translational platforms (Area C) into projects that establish proof-of-principle in non-clinical models and explore basic aspects of delivery and biosafety.
The established research groups are focusing on cell therapy, often in combination with genetic modification and tissue engineering. The latter activities include novel principles of laser technology, nanomanufacturing and cell processing. Our disease models cover a broad spectrum of lymphohaematopoietic, cardiac, pulmonary, hepatic and endocrine (such as diabetes mellitus) diseases.
The availability of induced pluripotent stem cells (iPSCs), not anticipated at the time the proposal was submitted (April 2006), has broadened the scope for the research conducted in Area B. Researchers in Area B are thus working closely together with the reprogramming groups in Area A to explore the potential of iPSCs in the development of advanced therapeutic medicinal products (ATMP). While we are confident that REBIRTH will constitute a leading centre for the development of iPSC-based ATMPs in Germany, we are also prepared to play our part in the intense international competition encountered in this highly dynamic field. Supported by the platforms of Area C, our current focus is to improve the efficiency of iPSC generation, to carefully study the biosafety of iPSC-derived cellbased products, and to explore alternative cell sources for organ regeneration. Research programmes that investigate modes of inducing tolerance and regenerating immunity in conditions of increased tolerance (i.e. cancer) are also incorporated into Area B. The most important organizational step taken was to bring together the major research groups and adjacent departments contributing to Area B in a new building (the Hans Borst Centre), fully equipped thanks to the financial support (including the funding of overheads) from the Cluster of Excellence. The groups working at this facility interact very closely. This has already resulted in numerous cooperative efforts, as documented in joint abstracts, manuscripts and the first published papers. The same applies to the collaboration with physicists and chemists developing novel enabling technologies. The newly formed research teams in Area B have also begun to demonstrate their potential with successful grant applications, many of them submitted in the context of regional, national and international scientific networks. Area B thus represents a platform with significant outreach beyond the Cluster itself.
In summary, most activities in Area B are well on track, with major contributions by junior investigators. The outcomes of the newly formed interactions within the Cluster of Excellence and beyond are expected to become even more visible during the next two years.
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