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  - Dotterweich, Julia
A1  - Tower, Robert J.
A1  - Brandl, Andreas
A1  - Müller, Marc
A1  - Hofbauer, Lorenz C.
A1  - Beilhack, Andreas
A1  - Ebert, Regina
A1  - Glüer, Claus C.
A1  - Tiwari, Sanjay
A1  - Schütze, Norbert
A1  - Jakob, Franz
T1  - The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease
JF  - PLoS One
N2  - Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone disease which could target the malignant cells and/or the surrounding cells of the tumor microenvironment. From these studies, the KISS1 receptor (KISS1R), a G-protein-coupled receptor known to play a role in the regulation of endocrine functions, was identified as a target gene that was upregulated on mesenchymal stem cells (MSCs) and osteoprogenitor cells (OPCs) when co-cultured with myeloma cells. To determine the potential of this receptor as a biomarker, in vitro and in vivo studies were performed with the KISS1R ligand, kisspeptin, conjugated with a fluorescent dye. In vitro microscopy showed binding of fluorescently-labeled kisspeptin to both myeloma cells as well as MSCs under direct co-culture conditions. Next, conjugated kisspeptin was injected into immune-competent mice containing myeloma bone lesions. Tumor-burdened limbs showed increased peak fluorescence compared to contralateral controls. These data suggest the utility of the KISS1R as a novel biomarker for multiple myeloma, capable of targeting both tumor cells and host cells of the tumor microenvironment.
KW  - multiple myeloma Lesions
KW  - fluorescence microscopy
KW  - biomarkers Myelomas
KW  - bone imaging
KW  - myeloma cells
KW  - fluorescent dyes
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146960
VL  - 11
IS  - 5
ER  -