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@ARTICLE{Blersch:258916,
      author       = {Blersch, Josephine and Kurkowsky, Birgit and Meyer-Berhorn,
                      Anja and Grabowska, Agnieszka Katarzyna and Feidt, Eva and
                      Junglas, Ellen and Roth, Wera and Stappert, Dominik and
                      Kuebelbeck, Armin and Denner, Philip and Fava, Eugenio},
      title        = {{A}n ex vivo human model for safety assessment of
                      immunotoxicity of engineered nanomaterials},
      reportid     = {DZNE-2023-00688},
      year         = {2023},
      abstract     = {The unique physicochemical properties of nanomaterials (NM)
                      and engineered nanomaterials (ENM) have pushed their use in
                      many applications ranging from medicine to the food
                      industry, textiles, and many more fields. Thus, human
                      exposure to NM and ENM is growing by the day. However, the
                      current toxicity tests do not reflect the special
                      characteristics of ENM and are not developed for ENM risk
                      assessment. Here we propose a high-throughput cell-based
                      assay using human peripheral blood mononuclear cells (PBMCs)
                      that can monitor the effects of NM and ENM on cytotoxicity
                      and innate immunity. The proposed assay is fully automated
                      and miniaturized, with excellent assay performance
                      parameters (Z-prime-score >0.5), amenable for large
                      screening campaigns in an industrial setting. Immunotoxicity
                      data for ENM safety assessment are collected in
                      dose-response format. At different states, multiparametric
                      readouts for cytotoxicity, and innate immunity are conducted
                      in a combinatorial method, avoiding ENM-induced bias by
                      endotoxin contamination. Integrating this high-dimensional
                      data allows (i) holistic safety assessment of immunotoxicity
                      effects caused by ENM, classifying safe and toxic ENM
                      phenotypes, and (ii) deconvolving mode of action of the ENM
                      effect on the PBMCs. As added value the data obtained can be
                      used to troubleshoot ENM or for a safe-by-design approach in
                      product development.},
      cin          = {AG Fava 2 ; AG Fava 2 / LAT},
      cid          = {I:(DE-2719)1040000 / I:(DE-2719)1040190},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/2023.06.29.547008},
      url          = {https://pub.dzne.de/record/258916},
}