title: In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles.
abstract: While research into the potential toxic properties of nanomaterials is now increasing, the area of developmental toxicity has remained relatively uninvestigated. The embryonic stem cell test is an in vitro screening assay used to investigate the embryotoxic potential of chemicals by determining their ability to inhibit differentiation of embryonic stem cells into spontaneously contracting cardiomyocytes. Four well characterized silica nanoparticles of various sizes were used to investigate whether nanomaterials are capable of inhibition of differentiation in the embryonic stem cell test. Nanoparticle size distributions and dispersion characteristics were determined before and during incubation in the stem cell culture medium by means of transmission electron microscopy (TEM) and dynamic light scattering. Mouse embryonic stem cells were exposed to silica nanoparticles at concentrations ranging from 1 to 100 microg/ml. The embryonic stem cell test detected a concentration dependent inhibition of differentiation of stem cells into contracting cardiomyocytes by two silica nanoparticles of primary size 10 (TEM 11) and 30 (TEM 34) nm while two other particles of primary size 80 (TEM 34) and 400 (TEM 248) nm had no effect up to the highest concentration tested. Inhibition of differentiation of stem cells occurred below cytotoxic concentrations, indicating a specific effect of the particles on the differentiation of the embryonic stem cells. The impaired differentiation of stem cells by such widely used particles warrants further investigation into the potential of these nanoparticles to migrate into the uterus, placenta and embryo and their possible effects on embryogenesis.
authors.affiliation: Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA, Bilthoven, The Netherlands. Margriet.Park@rivm.nl
authors.forename: Margriet V D Z
authors.initials: MV
authors.lastname: Park
authors.forename: Wijtske
authors.initials: W
authors.lastname: Annema
authors.forename: Anna
authors.initials: A
authors.lastname: Salvati
authors.forename: Anna
authors.initials: A
authors.lastname: Lesniak
authors.forename: Andreas
authors.initials: A
authors.lastname: Elsaesser
authors.forename: Clifford
authors.initials: C
authors.lastname: Barnes
authors.forename: George
authors.initials: G
authors.lastname: McKerr
authors.forename: C Vyvyan
authors.initials: CV
authors.lastname: Howard
authors.forename: Iseult
authors.initials: I
authors.lastname: Lynch
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.forename: Wim H
authors.initials: WH
authors.lastname: de Jong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006131:Growth Inhibitors / Q000633:toxicity*; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D006131:Growth Inhibitors; D012822:Silicon Dioxide