TY  - JOUR
A1  - Simsekyilmaz, Sakine
A1  - Liehn, Elisa A.
A1  - Weinandy, Stefan
A1  - Schreiber, Fabian
A1  - Megens, Remco T. A.
A1  - Theelen, Wendy
A1  - Smeets, Ralf
A1  - Jockenhövel, Stefan
A1  - Gries, Thomas
A1  - Möller, Martin
A1  - Klee, Doris
A1  - Weber, Christian
A1  - Zernecke, Alma
T1  - Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice
JF  - PLoS ONE
N2  - Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE\(^{-/-}\) carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.
KW  - carotid arteries
KW  - polymers
KW  - stent implantation
KW  - coatings
KW  - endothelial cells
KW  - mice
KW  - fluorescence microscopy
KW  - stem cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179745
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Manukjan, Georgi
A1  - Ripperger, Tim
A1  - Venturini, Letizia
A1  - Stadler, Michael
A1  - Göhring, Gudrun
A1  - Schambach, Axel
A1  - Schlegelberger, Brigitte
A1  - Steinemann, Doris
T1  - GABP is necessary for stem/progenitor cell maintenance and myeloid differentiation in human hematopoiesis and chronic myeloid leukemia
JF  - Stem Cell Research
N2  - Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of murine hematopoietic and leukemic stem cells. Here, we report the consequences of functional impairment of GABP in human hematopoietic and in leukemic stem/progenitor cells. Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34\(^{+}\) hematopoietic stem/progenitor cells obtained from healthy donors. Moreover, drastically reduced clonogenic capacity of leukemic stem/progenitor cells isolated from bone marrow aspirates of chronic myeloid leukemia (CML) patients underlines the importance of GABP on stem/progenitor cell maintenance and confirms the relevance of GABP for human myelopoiesis in healthy and diseased states.
KW  - GABP
KW  - stem cells
KW  - human hematopoiesis
KW  - leukemia
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168165
VL  - 16
IS  - 3
ER  -