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Therapeutic angiogenesis

Prof. Dr. Günter Finkenzeller

Vascularization plays an important role in the engineering of complex tissue substitutes, because without sufficient vascularization, implants will not survive the  postimplantational phase, due to the formation of tissue hypoxia. Cells inside the implants are absolutely dependent on the delivery of nutrients and oxygen. In our projekts aiming at the improvement of vascularization of replacement tissues, we pursue gene- as well as cell-therapeutic strategies. In the context of cell therapy, we have seen that neovascularization can be induced by co-implantation of umbilical vein endothelial cells (HUVECs) or by co-implantation of cord blood derived endothelial progenitor cells (EPCs). In both cases, implanted endothelial cells can form blood vessels that are stabilized by smooth muscle cells and that are able to anastomose with the blood vessels of the recipient. In gene-therapeutic strategies, we focused our interest on the master transcription factor “Hypoxia induced factor-1 alpha” (Hif-1alpha) which is known to orchestrate gene expression programs that are associated with blood vessel formation. In this context, we have seen that adenoviral overexpression of Hif-1alpha improves vasculogenesis-related cell parameters in EPCs, and also improves in vivo blood vessel formation. Moreover, Hif-1alpha overexpression in MSCs showed positive effects on cell-autonomous parameters such as proliferation, migration, cell survival and expression of proangiogenic genes. Individual projects within this research field are supported by the German Research Community (DFG) and the Doktor Robert Pfleger Foundation.