title: Size-Dependent Toxicity of Gold Nanoparticles on Human Embryonic Stem Cells and Their Neural Derivatives.
abstract: This study explores the use of human embryonic stem cells (hESCs) for assessing nanotoxicology, specifically, the effect of gold nanoparticles (AuNPs) of different core sizes (1.5, 4, and 14 nm) on the viability, pluripotency, neuronal differentiation, and DNA methylation of hESCs. The hESCs exposed to 1.5 nm thiolate-capped AuNPs exhibit loss of cohesiveness and detachment suggesting ongoing cell death at concentrations as low as 0.1 μg mL(-1). The cells exposed to 1.5 nm AuNPs at this concentration do not form embryoid bodies but rather disintegrate into single cells within 48 h. Cell death caused by 1.5 nm AuNPs also occur in hESC-derived neural progenitor cells. None of the other nanoparticles exhibit toxic effects on the hESCs at concentrations as high as 10 μg mL(-1) during a 19 d neural differentiation period. Thiolate-capped 4 nm AuNPs at 10 μg mL(-1) cause a dramatic decrease in global DNA methylation (5 mC) and a corresponding increase in global DNA hydroxymethylation (5 hmC) of the hESC's DNA in only 24 h. This work identifies a type of AuNPs highly toxic to hESCs and demonstrates the potential of hESCs in predicting nanotoxicity and characterizing their ability to alter the DNA methylation and hydroxymethylation patterns in the cells.
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, 275 East Hancock Road, Detroit, MI, 48201, USA.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Senut
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI, 48202, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI, 48202, USA.
authors.forename: Fangchao
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, 275 East Hancock Road, Detroit, MI, 48201, USA.
authors.forename: Arko
authors.initials: A
authors.lastname: Sen
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, 275 East Hancock Road, Detroit, MI, 48201, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Ruden
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI, 48202, USA.
authors.forename: Guangzhao
authors.initials: G
authors.lastname: Mao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry; D058732:Embryoid Bodies / Q000166:cytology; D004705:Endocytosis / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects; D010316:Particle Size; D039904:Pluripotent Stem Cells / Q000166:cytology
chemical_list: D050091:Dendrimers; D006046:Gold
keywords: assays; gold; human embryonic stem cells; nanoparticles; toxicology