title: Silver nanoparticles: evaluation of DNA damage, toxicity and functional impairment in human mesenchymal stem cells.
abstract: Silver nanoparticles (Ag-NPs) are the most frequent commercialized nanomaterial currently. Due to a distinct lack of information on hazardous properties of Ag-NPs in human cells, a study was conducted to evaluate Ag-NP induced DNA damage, cell death and functional impairment in human mesenchymal stem cells (hMSCs). Initially, Ag-NPs and their cellular distribution were characterized by transmission electron microscopy (TEM). Ag-NPs were exposed to hMSCs for 1, 3 and 24h. Cytotoxicity was measured by the trypan blue exclusion test and the fluorescein-diacetate test, DNA damage was evaluated by the comet assay and chromosomal aberration test. Cytokine release of IL-6, IL-8 and VEGF was observed using the ELISA technique. Additionally, hMSC migration capability was tested in a transwell system. TEM revealed a Ag-NP distribution to cytoplasm and nucleus. Cytotoxic effects were seen at concentrations of 10 μg/ml for all test exposure periods. Both, comet assay and chromosomal aberration test showed DNA damage after 1, 3, and 24h at 0.1 μg/ml. A significant increase of IL-6, IL-8 and VEGF release indicates hMSC activation. Migration ability was not impaired at subtoxic concentrations. In conclusion, we demonstrated cyto- and genotoxic potential of Ag-NPs in hMSCs at significantly higher concentrations as compared to antimicrobial effective levels.
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hackenberg
authors.forename: Agmal
authors.initials: A
authors.lastname: Scherzed
authors.forename: Michael
authors.initials: M
authors.lastname: Kessler
authors.forename: Silke
authors.initials: S
authors.lastname: Hummel
authors.forename: Antje
authors.initials: A
authors.lastname: Technau
authors.forename: Katrin
authors.initials: K
authors.lastname: Froelich
authors.forename: Christian
authors.initials: C
authors.lastname: Ginzkey
authors.forename: Christian
authors.initials: C
authors.lastname: Koehler
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
authors.forename: Norbert
authors.initials: N
authors.lastname: Kleinsasser
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D053768:Metal Nanoparticles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D012834:Silver