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Conclusion 46 5.

Conclusion 46 5. Conclusions and Outlook We conclude that the oxygen level during cell culture has a profound impact on the cell characteristics, cell migration and integrin expression of hMSCs. Hypoxic cell culture conditions enhance cell proliferation, cell metabolism and prolong stemness of human mesenchymal stem cells in vitro. Furthermore, hypoxia during cell culture leads to increased cell migration. This is especially pronounced on collagen I and laminin coated surfaces. Additionally, hypoxia leads to differences in integrin expression. In a future study, we will evaluate oxygen-dependent differences in the cytoskeleton such as actin fibres and how these changes possibly affect biophysical characteristics of the cell. Furthermore, we will increase the efforts to understand oxygen dependent differences in migration and invasion of hMSCs, since these are the prerequisite for tissue repair. Finally, we will enlight selected integrin pathways. Especially the correlation between HIF-1α and integrin expression is of great interest, since HIF-1α is a key factor in response to hypoxia. We thereby hope to reveal new information concerning cell-cell or cell-matrix interaction and communication in hypoxic conditions.

References 47 6. References 1. BECKER,A.J., McCULLOCH,E.A. & TILL,J.E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197, 452-454 (1963). 2. Saruwatari,L. et al. Osteoblasts generate harder, stiffer, and more delamination-resistant mineralized tissue on titanium than on polystyrene, associated with distinct tissue micro- and ultrastructure. J. Bone Miner. Res. 20, 2002- 2016 (2005). 3. Scholer,H.R. [The potential of stem cells. A status update]. Bundesgesundheitsblatt. Gesundheitsforschung. Gesundheitsschutz. 47, 565-577 (2004). 4. Laurencin,C., Khan,Y. & El Amin,S.F. Bone graft substitutes. Expert. Rev. Med. Devices 3, 49-57 (2006). 5. Drosse,I. et al. Tissue engineering for bone defect healing: an update on a multi-component approach. Injury 39 Suppl 2, S9-20 (2008). 6. Langer,R. & Vacanti,J.P. Tissue engineering. Science 260, 920-926 (1993). 7. Rustad,K.C., Sorkin,M., Levi,B., Longaker,M.T. & Gurtner,G.C. Strategies for organ level tissue engineering. Organogenesis. 6, 151-157 (2010). 8. Schieker,M. & Mutschler,W. [Bridging posttraumatic bony defects. Established and new methods]. Unfallchirurg 109, 715-732 (2006). 9. Leukers,B. et al. Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing. J. Mater. Sci. Mater. Med. 16, 1121-1124 (2005). 10. Friedenstein,A.J., Piatetzky-Shapiro,I.I. & Petrakova,K.V. Osteogenesis in transplants of bone marrow cells. J. Embryol. Exp. Morphol. 16, 381-390 (1966). 11. Panetta,N.J., Gupta,D.M., Quarto,N. & Longaker,M.T. Mesenchymal cells for skeletal tissue engineering. Panminerva Med. 51, 25-41 (2009). 12. Caplan,A.I. Mesenchymal stem cells. J. Orthop. Res. 9, 641-650 (1991). 13. Pittenger,M.F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147 (1999). 14. Dominici,M. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315-317 (2006). 15. Caplan,A.I. What's in a name? Tissue Eng Part A 16, 2415-2417 (2010).

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