title: Effects of silica and titanium oxide particles on a human neural stem cell line: morphology, mitochondrial activity, and gene expression of differentiation markers.
abstract: Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not clear whether the penetrated nanoparticles affect neurogenesis or brain function. To evaluate its effects on neural stem cells, we assayed a human neural stem cell (hNSCs) line exposed in vitro to three types of silica particles (30 nm, 70 nm, and <44 µm) and two types of titanium oxide particles (80 nm and < 44 µm). Our results show that hNSCs aggregated and exhibited abnormal morphology when exposed to the particles at concentrations = 0.1 mg/mL for 7 days. Moreover, all the particles affected the gene expression of Nestin (stem cell marker) and neurofilament heavy polypeptide (NF-H, neuron marker) at 0.1 mg/mL. In contrast, only 30-nm silica particles at 1.0 mg/mL significantly reduced mitochondrial activity. Notably, 30-nm silica particles exhibited acute membrane permeability at concentrations =62.5 µg/mL in 24 h. Although these concentrations are higher than the expected concentrations of nanoparticles in the brain from in vivo experiments in a short period, these thresholds may indicate the potential toxicity of accumulated particles for long-term usage or continuous exposure.
authors.affiliation: Division of Molecular Cell Biology, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan. kfujioka@jikei.ac.jp.
authors.forename: Kouki
authors.initials: K
authors.lastname: Fujioka
authors.affiliation: Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. hanada@ri.ncgm.go.jp.
authors.forename: Sanshiro
authors.initials: S
authors.lastname: Hanada
authors.affiliation: Department of Anatomy, Toho University, Tokyo 143-8540, Japan. yuriko.inoue@med.toho-u.ac.jp.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Electrical and Electronic Engineering, Tokyo Denki University, Tokyo 120-8551,Japan. satok@mail.dendai.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Electrical and Electronic Engineering, Tokyo Denki University, Tokyo 120-8551,Japan. hirakuri@mail.dendai.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirakuri
authors.affiliation: Medical Engineering Laboratory, Research Center for Medical Science,The Jikei University School of Medicine, Tokyo 105-8461, Japan. kshiraishi@jikei.ac.jp.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. fkanaya@acc.ncgm.go.jp.
authors.forename: Fumihide
authors.initials: F
authors.lastname: Kanaya
authors.affiliation: Division of Molecular Cell Biology, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan. ikedak@jikei.ac.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Division of Molecular Cell Biology, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan. ree-chicochamaro@jikei.ac.jp.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Usui
authors.affiliation: Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. ykenji@hosp.ncgm.go.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Medical Research Institute, Chung-Ang University College of Medicine, Seoul 440-746, Korea. sukim@mail.ubc.ca.
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.affiliation: Division of Molecular Cell Biology, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan. manome@jikei.ac.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Manome
mesh_terms: D002460:Cell Line; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D053758:Nanoparticles; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology*; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D064231:Nestin; D016900:Neurofilament Proteins; C051774:neurofilament protein H; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium