title: Functional responses of human adipose tissue-derived mesenchymal stem cells to metal oxide nanoparticles in vitro.
abstract: Nanoparticles (NPs) are frequently applied in biomedical applications. The use of human mesenchymal stem cells (hMSC) in biomedicine is pivotal, especially in oncology and tissue engineering. Titanium dioxide (TiO2) and zinc oxide (ZnO) NPs are interesting agents in experimental oncology and stem cells are discussed to be a potential vehicle for NPs to tumor sites. However, little is known about hazardous effects of NPs in hMSC. The aim of the present study was to analyze functional impairment of hMSC by ZnO- and TiO2-NPs. Cytotoxic effects of NPs were evaluated by the MTT-assay. Furthermore, multi-differentiation capacity, spheroid formation and migration were assessed. The immunophenotype was observed by flow cytometry. Cytotoxic effects were observed at 625 nM ZnO-NPs whereas no cytotoxicity was seen in hMSC by TiO2-NPs. The differentiation capacity of hMSC into osteogenic and adipose lineages was unchanged. A long-term period cultivation of hMSC for 3 weeks after NP exposure revealed a persistence of NPs in the cytoplasm. The migration capability was impaired whereas the ability to form spheroids was not affected. Flow cytometric analysis revealed distinct alteration of cell surface markers CD 90 and CD 73. Major functional properties of hMSC were unaffected by TiO2- and ZnO-NPs. However, restricted migration might critically influence wound healing capacity. Further information is needed to assess the clinical impact of these findings.
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hackenberg
authors.forename: Agmal
authors.initials: A
authors.lastname: Scherzed
authors.forename: Antje
authors.initials: A
authors.lastname: Technau
authors.forename: Katrin
authors.initials: K
authors.lastname: Froelich
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
authors.forename: Norbert
authors.initials: N
authors.lastname: Kleinsasser
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects; D014025:Titanium / Q000633:toxicity*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D015415:Biomarkers; C009495:titanium dioxide; D014025:Titanium; D015034:Zinc Oxide