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A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles

A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles

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Prüfsumme: MD5:745b7050f59cd8cfc809c4c64e308c84

HÖLTING, Lisa, Benjamin SCHEINHARDT, Olesja BONDARENKO, Stefan SCHILDKNECHT, Marion KAPITZA, Vivek TANAVDE, Betty TAN, Qian Yi LEE, Stefan MECKING, Marcel LEIST, Suzanne KADEREIT, 2013. A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles. In: Archives of Toxicology. 87(4), pp. 721-733. ISSN 0340-5761. eISSN 1432-0738

@article{Holting2013-043-dim-24346, title={A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles}, year={2013}, doi={10.1007/s00204-012-0984-2}, number={4}, volume={87}, issn={0340-5761}, journal={Archives of Toxicology}, pages={721--733}, author={Hölting, Lisa and Scheinhardt, Benjamin and Bondarenko, Olesja and Schildknecht, Stefan and Kapitza, Marion and Tanavde, Vivek and Tan, Betty and Lee, Qian Yi and Mecking, Stefan and Leist, Marcel and Kadereit, Suzanne} }

Leist, Marcel A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles eng Kadereit, Suzanne Kadereit, Suzanne Leist, Marcel Bondarenko, Olesja Kapitza, Marion Tanavde, Vivek Hölting, Lisa Schildknecht, Stefan Bondarenko, Olesja deposit-license Lee, Qian Yi Scheinhardt, Benjamin Mecking, Stefan Scheinhardt, Benjamin Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood–brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6<sup>+</sup> precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT. Kapitza, Marion Archives of toxicology ; 87 (2013), 4. - S. 721-733 2013-04 Mecking, Stefan Tan, Betty 2014-03-31T22:25:12Z Tanavde, Vivek Lee, Qian Yi Schildknecht, Stefan 2013-09-11T08:48:06Z Hölting, Lisa Tan, Betty

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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