Effects of Silica and Titanium Oxide Particles on a Human Neural Stem Cell Line: Morphology, Mitochondrial Activity, and Gene Expression of Differentiation Markers

International Journal of Molecular Sciences

Kouki Fujioka²  Sanshiro Hanada³  Yuriko Inoue⁵  Keisuke Sato⁶  Kenji Hirakuri⁶  Kouichi Shiraishi⁴  Fumihide Kanaya³  Keiichi Ikeda²  Ritsuko Usui²  Kenji Yamamoto³  Seung U. Kim¹ 

[1] Medical Research Institute, Chung-Ang University College of Medicine, Seoul 440-746, Korea; E-Mail:;Division of Molecular Cell Biology, Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan; E-Mails:;Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; E-Mails:;Medical Engineering Laboratory, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan; E-Mail:;Department of Anatomy, Toho University, Tokyo 143-8540, Japan; E-Mail:;Department of Electrical and Electronic Engineering, Tokyo Denki University, Tokyo 120-8551, Japan; E-Mails:

关键词: silica;    titanium oxide;    nano;    toxicity;    neural stem cell;    neural progenitor cell;    differentiation;   

DOI  :  10.3390/ijms150711742

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.