@article{RadeloffWeissHagenetal.2021,
  author    = {Radeloff, Katrin and Weiss, Dorothee and Hagen, Rudolf and Kleinsasser, Norbert and Radeloff, Andreas},
  title     = {Differentiation behaviour of adipose-derived stromal cells (ASCs) seeded on polyurethane-fibrin scaffolds in vitro and in vivo},
  series = {Biomedicines},
  volume    = {9},
  journal   = {Biomedicines},
  number    = {8},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9080982},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245030},
  year      = {2021},
  abstract  = {Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.},
  language  = {en}
}
@article{RadeloffRamosTiradoHaddadetal.2021,
  author    = {Radeloff, Katrin and Ramos Tirado, Mario and Haddad, Daniel and Breuer, Kathrin and M{\"u}ller, Jana and Hochmuth, Sabine and Hackenberg, Stephan and Scherzad, Agmal and Kleinsasser, Norbert and Radeloff, Andreas},
  title     = {Superparamagnetic iron oxide particles (VSOPs) show genotoxic effects but no functional impact on human adipose tissue-derived stromal cells (ASCs)},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {2},
  issn      = {1996-1944},
  doi       = {10.3390/ma14020263},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222970},
  year      = {2021},
  abstract  = {Adipose tissue-derived stromal cells (ASCs) represent a capable source for cell-based therapeutic approaches. For monitoring a cell-based application in vivo, magnetic resonance imaging (MRI) of cells labeled with iron oxide particles is a common method. It is the aim of the present study to analyze potential DNA damage, cytotoxicity and impairment of functional properties of human (h)ASCs after labeling with citrate-coated very small superparamagnetic iron oxide particles (VSOPs). Cytotoxic as well as genotoxic effects of the labeling procedure were measured in labeled and unlabeled hASCs using the MTT assay, comet assay and chromosomal aberration test. Trilineage differentiation was performed to evaluate an impairment of the differentiation potential due to the particles. Proliferation as well as migration capability were analyzed after the labeling procedure. Furthermore, the labeling of the hASCs was confirmed by Prussian blue staining, transmission electron microscopy (TEM) and high-resolution MRI. Below the concentration of 0.6 mM, which was used for the procedure, no evidence of genotoxic effects was found. At 0.6 mM, 1 mM as well as 1.5 mM, an increase in the number of chromosomal aberrations was determined. Cytotoxic effects were not observed at any concentration. Proliferation, migration capability and differentiation potential were also not affected by the procedure. Labeling with VSOPs is a useful labeling method for hASCs that does not affect their proliferation, migration and differentiation potential. Despite the absence of cytotoxicity, however, indications of genotoxic effects have been demonstrated.},
  language  = {en}
}
@article{RadeloffRadeloffTiradoetal.2019,
  author    = {Radeloff, Katrin and Radeloff, Andreas and Tirado, Mario Ramos and Scherzad, Agmal and Hagen, Rudolf and Kleinsasser, Norbert H. and Hackenberg, Stephan},
  title     = {Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells},
  series = {Materials},
  volume    = {12},
  journal   = {Materials},
  number    = {1823},
  doi       = {10.3390/ma12111823},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224779},
  pages     = {1-14},
  year      = {2019},
  abstract  = {Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 mu g/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.},
  language  = {en}
}
@article{RadeloffRadeloffRamosTiradoetal.2020,
  author    = {Radeloff, Katrin and Radeloff, Andreas and Ramos Tirado, Mario and Scherzad, Agmal and Hagen, Rudolf and Kleinsasser, Norbert H. and Hackenberg, Stephan},
  title     = {Toxicity and functional impairment in human adipose tissue-derived stromal cells (hASCs) following long-term exposure to very small iron oxide particles (VSOPs)},
  series = {Nanomaterials},
  volume    = {10},
  journal   = {Nanomaterials},
  number    = {4},
  issn      = {2079-4991},
  doi       = {10.3390/nano10040741},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203676},
  year      = {2020},
  abstract  = {Magnetic nanoparticles (NPs), such as very small iron oxide NPs (VSOPs) can be used for targeted drug delivery, cancer treatment or tissue engineering. Another important field of application is the labelling of mesenchymal stem cells to allow in vivo tracking and visualization of transplanted cells using magnetic resonance imaging (MRI). For these NPs, however, various toxic effects, as well as functional impairment of the exposed cells, are described. The present study evaluates the influence of VSOPs on the multilineage differentiation ability and cytokine secretion of human adipose tissue derived stromal cells (hASCs) after long-term exposure. Human ASCs were labelled with VSOPs, and the efficacy of the labelling was documented over 4 weeks in vitro cultivation of the labelled cells. Unlabelled hASCs served as negative controls. Four weeks after labelling, adipogenic and osteogenic differentiation was histologically evaluated and quantified by polymerase chain reaction (PCR). Changes in gene expression of IL-6, IL-8, VEGF and caspase 3 were determined over 4 weeks. Four weeks after the labelling procedure, labelled and unlabelled hASCs did not differ in the gene expression of IL-6, IL-8, VEGF and caspase 3. Furthermore, the labelling procedure had no influence on the multidifferentiation ability of hASC. The percentage of labelled cells decreased during in vitro expansion over 4 weeks. Labelling with VSOPs and long-term intracellular disposition probably have no influence on the physiological functions of hASCs. This could be important for the future in vivo use of iron oxide NPs.},
  language  = {en}
}