@article{ScherzadMeyerIckrathetal.2019, author = {Scherzad, Agmal and Meyer, Till and Ickrath, Pascal and Gehrke, Thomas Eckhart and Bregenzer, Maximillian and Hagen, Rudolf and Dembski, Sofia and Hackenberg, Stephan}, title = {Cultivation of hMSCs in human plasma prevents the cytotoxic and genotoxic potential of ZnO-NP in vitro}, series = {Applied Sciences}, volume = {9}, journal = {Applied Sciences}, number = {23}, issn = {2076-3417}, doi = {10.3390/app9234994}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193063}, year = {2019}, abstract = {Zinc oxide nanoparticles (ZnO-NPs) are commonly used for industrial applications. Consequently, there is increasing exposure of humans to them. The in vitro analysis of cytotoxicity and genotoxicity is commonly performed under standard cell culture conditions. Thus, the question arises of how the results of genotoxicity and cytotoxicity experiments would alter if human plasma was used instead of cell culture medium containing of fetal calf serum (FCS). Human mesenchymal stem cells (hMSCs) were cultured in human plasma and exposed to ZnO-NPs. A cultivation in expansion medium made of DMEM consisting 10\% FCS (DMEM-EM) served as control. Genotoxic and cytotoxic effects were evaluated with the comet and MTT assay, respectively. hMSC differentiation capacity and ZnO-NP disposition were evaluated by histology and transmission electron microscopy (TEM). The protein concentration and the amount of soluble Zn2+ were measured. The cultivation of hMSCs in plasma leads to an attenuation of genotoxic and cytotoxic effects of ZnO-NPs compared to control. The differentiation capacity of hMSCs was not altered. The TEM showed ZnO-NP persistence in cytoplasm in both groups. The concentrations of protein and Zn2+ were higher in plasma than in DMEM-EM. In conclusion, the cultivation of hMSCs in plasma compared to DMEM-EM leads to an attenuation of cytotoxicity and genotoxicity in vitro.}, language = {en} } @article{MeyerStoethMoratinetal.2021, author = {Meyer, Till Jasper and St{\"o}th, Manuel and Moratin, Helena and Ickrath, Pascal and Herrmann, Marietta and Kleinsasser, Norbert and Hagen, Rudolf and Hackenberg, Stephan and Scherzad, Agmal}, title = {Cultivation of head and neck squamous cell carcinoma cells with wound fluid leads to cisplatin resistance via epithelial-mesenchymal transition induction}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms22094474}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258722}, year = {2021}, abstract = {Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.}, language = {en} } @article{MoratinIckrathScherzadetal.2021, author = {Moratin, Helena and Ickrath, Pascal and Scherzad, Agmal and Meyer, Till Jasper and Naczenski, Sebastian and Hagen, Rudolf and Hackenberg, Stephan}, title = {Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes}, series = {Nanomaterials}, volume = {11}, journal = {Nanomaterials}, number = {3}, issn = {2079-4991}, doi = {10.3390/nano11030629}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234016}, year = {2021}, abstract = {Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed.}, language = {en} }