Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

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Research Since the late 1980s, Tissue Engineering has been one of the key technologies in regenerative medicine. Regarding bone tissue, an approach based on scaffolds as carriers for patient’s own cells and suitable growth factors has been proposed. Our group focuses on engineering bioartificial bone tissues and vascularisation models. The combination of smart biomaterials, osteoinductive factors and osteogenic cells lead to new perspectives in bone regeneration therapy. Endothelial cell (EC) culture, osteoblast (OB) culture and marrow stromal cell (MSC) culture are utilised in vitro. Furthermore, we use in vivo subcutaneous models and vascularisation models (e.g. arteriovenous loop model) in rats (in cooperation with Franz-Penzoldt-Zentrum). Bone Tissue Engineering Bone defects and impaired bone healing represent substantial challenges in reconstructive surgery. By bone tissue engineering it may be possible to heal complex bone defects in the future. Our group works on the application of novel biomaterials, innovative cell culture models and co-cultures. Induction of bone formation in biphasic calcium phosphate ceramics Subha N. Rath, Leonie Strobel, Ulrich Kneser In cooperation with the Institute of Materials Science (Prof. P. Greil), Erlangen Novel biphasic calcium phosphate (BCP) matrices were generated by 3D printing and high porosity was achieved by starch consolidation (Department of Materials Science (Glass and Ceramics), FAU Erlangen). This project aimed to characterise the porous BCP scaffold’s properties and the interaction of osteogenic cells and growth factors under in vitro and in vivo conditions. Bioreactors are advised for improved cell survival, as they are able to provide a controlled flow through the scaffold. Osteogenic cells (rat primary osteoblasts (OB) and bone marrow stromal cells (MSCs)) were isolated, cultured and seeded onto 3D scaffolds. Samples in static culture without osteoinduction, static culture with osteoinduction and dynamic culture with osteoinduction were compared over 6 weeks. Analyses showed that a continuous flow bioreactor not only preserves the number of osteogenic cells, but also keeps their differentiation ability in balance providing a suitable cell-seeded scaffold product for applications in regenerative medicine (Rath, Strobel et al. 2012). Furthermore, these very BCP scaffolds were evaluated in vivo. Five differently treated constructs were implanted subcutaneously in syngeneic male Lewis rats: 127
plain BCP constructs, constructs pre-treated with BMP-2, seeded with osteoblasts (OB), seeded with OB and BMP-2 and constructs with OB that were pre-cultivated in a flow bioreactor for 6 weeks. Specimens were explanted and subjected to histology and molecular biological analysis after 2, 4 and 6 weeks. All explanted constructs were invaded by fibrovascular tissue. Samples with both OB and BMP-2 demonstrated higher osteogenic gene expression and significantly increased bone formation compared to all other groups. Pre-cultivation in the flow bioreactor induced bone formation comparable with the freshly seeded group. In summary, the combination of OB and BMP-2 enhanced bone formation in the novel ceramic scaffolds (Strobel, Rath et al. 2012). This work was supported by the German Research Foundation (DFG). Rath SN, Strobel LA, Meier AK. 2012, Osteoinduction of osteoblasts and bone marrow stromal cells in 3D BCP scaffolds: the effect of bioreactor on cell survival and differentiation, Journal of Cellular and Molecular Medicine; 2012 Feb 3. doi: 10.1111/j.1582-4934.2012.01545.x. Strobel LA, Rath SN, Maier AK. 2012, Induction of Bone Formation in Biphasic Calcium Phosphate Scaffolds by Bone Morphogenetic Protein-2 and Primary Osteoblasts Journal of Tissue Engineering and Regenerative Medicine; (accepted) Haematoxylin-eosin (HE) staining of an explanted biphasic calcium phosphate (BCP) scaffold at 6 weeks after subcutaneous implantation. The scaffold was seeded with primary osteoblasts previous to implantation. Newly formed bone areas (arrows) are visible in the pores of the BCP construct. Human marrow stromal cells (hMSCs) on innovative bioglass scaffolds* Subha N. Rath, Daniel Hiller, Ulrich Kneser In cooperation with the Institute of Biomaterials (Prof. A. Boccaccini), Erlangen The aim of this study is to analyse hMSCs response to new bioactive copper-doped glass scaffolds. 45S5 bioglass scaffolds containing different concentrations of copper are provided by the Institute of Biomaterials. First, these scaffolds were evaluated regarding copper and bioactive ion release in vitro. For this purpose, we observed 2dimensional cell culture in vicinity to bioactive glass. The constructs proved non-toxic and provided continuous release of copper (depending on the initial copperconcentration). Furthermore, scaffolds are seeded with hMSCs and evaluated under 128
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Nikolaus-Fiebiger-Zentrum für Mole
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PREFACE Our present report covers t
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SCIENTIFIC ADVISORY BOARD The scien
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Financial Concept (Running Costs) R
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DEPARTMENT OF EXPERIMENTAL MEDICINE
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Research projects: I. Analyzing the
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osteoclast activity, we cannot rule
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Previously we have shown that cellu
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The proposed studies will provide n
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We recently introduced Ucma (Upper
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Park J, Bauer S, Schlegel KA, Neuka
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Research Hypertension is the primar
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accessory protein of the H+ vacuola
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Searle, J., Mockel, M., Gwosc, S.,
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DEPARTMENT OF EXPERIMENTAL MEDICINE
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Research Our group analyses molecul
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We found that the transcriptional r
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Fig. 1 Dual functional role of Amer
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HIF target gene expression in renal
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2009 Wacker, I., Sachs, M., Knaup,
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Andreas Brandl* Sebastian Dütting*
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microRNAs in lymphocytes in health
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Function of EFhd1 and EFhd2 in B ce
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mainly expressed on phagocytes, fun
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Lang, V. R., Mielenz, D., Neubert,
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TRAINING OF GRADUATE AND MEDICAL ST
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Research Our research focus lies on
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During the last 3 years we had succ
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Adoptive transfer of memory B cells
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transplantation represents a novel,
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passive immunization for prevention
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Weisel, F.J., U.K. Appelt, A.M. Sch
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IZKF Junior Group III BMBF Research
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Figure 1: Induced pluripotent stem
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oligomerizing mutant (α-syn mut, F
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INTERDISCILINARY CENTER OF CLINICAL
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Research Primary essential hyperten
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hypertonic interstitial fluid accum
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its soluble receptor sVEGFR3). This
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Page 83 and 84: 2011 Slagman MC, Kwakernaak AJ, Yaz
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Page 93 and 94: 13. Krönke G, Uderhardt S, Kim KA,
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Page 125 and 126: Matthias Koch Franziska Cipa Melani
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Page 129 and 130: Books and Reviews Gelse K, Beyer C.
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Page 137 and 138: Original Articles Rath SN, Strobel
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Page 143 and 144: Fig. 3 The nuclear receptor PPARβ
Page 145 and 146: Books and Reviews Scholtysek C, Kr
Page 147 and 148: Elke Nolte geb. Löprich, Dipl. Bio
Page 149 and 150: prognosis and metastases of prostat
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Page 153 and 154: DEPARTMENT OF INTERNAL MEDICINE 5 (
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Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

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