In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles

Margriet VDZ Park, Wijtske Annema, Anna Salvati, Anna Lesniak, Andreas Elsaesser, Clifford Barnes, George McKerr, Vyvyan Howard, Iseult Lynch, Kenneth A Dawson, Aldert H Piersma, Wim H de Jong

Research output: Contribution to journalArticle

105 Citations (Scopus)

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 mu g/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. (C) 2009 Elsevier Inc. All rights reserved.
LanguageEnglish
Pages108-116
JournalToxicology and Applied Pharmacology
Volume240
Issue number1
DOIs
Publication statusPublished - Oct 2009

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Toxicity Tests
Embryonic Stem Cells
Transmission Electron Microscopy
Silicon Dioxide
Nanoparticles
Cell Differentiation
Stem Cells
Nanostructures
Cardiac Myocytes
Poisons
Particle Size
Placenta
Uterus
Embryonic Development
Culture Media
Embryonic Structures
Cell Culture Techniques
In Vitro Techniques
Research

Cite this

Park, M. VDZ., Annema, W., Salvati, A., Lesniak, A., Elsaesser, A., Barnes, C., ... de Jong, W. H. (2009). In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. Toxicology and Applied Pharmacology, 240(1), 108-116. https://doi.org/10.1016/j.taap.2009.07.019
Park, Margriet VDZ ; Annema, Wijtske ; Salvati, Anna ; Lesniak, Anna ; Elsaesser, Andreas ; Barnes, Clifford ; McKerr, George ; Howard, Vyvyan ; Lynch, Iseult ; Dawson, Kenneth A ; Piersma, Aldert H ; de Jong, Wim H. / In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. In: Toxicology and Applied Pharmacology. 2009 ; Vol. 240, No. 1. pp. 108-116.
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Park, MVDZ, Annema, W, Salvati, A, Lesniak, A, Elsaesser, A, Barnes, C, McKerr, G, Howard, V, Lynch, I, Dawson, KA, Piersma, AH & de Jong, WH 2009, 'In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles', Toxicology and Applied Pharmacology, vol. 240, no. 1, pp. 108-116. https://doi.org/10.1016/j.taap.2009.07.019

In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. / Park, Margriet VDZ; Annema, Wijtske; Salvati, Anna; Lesniak, Anna; Elsaesser, Andreas; Barnes, Clifford; McKerr, George; Howard, Vyvyan; Lynch, Iseult; Dawson, Kenneth A; Piersma, Aldert H; de Jong, Wim H.

In: Toxicology and Applied Pharmacology, Vol. 240, No. 1, 10.2009, p. 108-116.

Research output: Contribution to journalArticle

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AU - Park, Margriet VDZ

AU - Annema, Wijtske

AU - Salvati, Anna

AU - Lesniak, Anna

AU - Elsaesser, Andreas

AU - Barnes, Clifford

AU - McKerr, George

AU - Howard, Vyvyan

AU - Lynch, Iseult

AU - Dawson, Kenneth A

AU - Piersma, Aldert H

AU - de Jong, Wim H

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N2 - 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 mu g/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. (C) 2009 Elsevier Inc. All rights reserved.

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