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Article

Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening

1
BioTalentum Ltd., H-2100 Gödöllő, Hungary
2
Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, H-1117 Budapest, Hungary
3
Molecular Animal Biotechnology Laboratory, Szent István University, H-2101 Gödöllő, Hungary
4
Translational Biomedicine Institute, University of Szeged, H-6720 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1122; https://doi.org/10.3390/cells9051122
Received: 26 March 2020 / Revised: 27 April 2020 / Accepted: 29 April 2020 / Published: 1 May 2020
(This article belongs to the Special Issue 3D Stem Cell Culture)
We present a hiPSC-based 3D in vitro system suitable to test neurotoxicity (NT). Human iPSCs-derived 3D neurospheres grown in 96-well plate format were characterized timewise for 6-weeks. Changes in complexity and homogeneity were followed by immunocytochemistry and transmission electron microscopy. Transcriptional activity of major developmental, structural, and cell-type-specific markers was investigated at weekly intervals to present the differentiation of neurons, astrocytes, and oligodendrocytes. Neurospheres were exposed to different well-known toxicants with or without neurotoxic effect (e.g., paraquat, acrylamide, or ibuprofen) and examined at various stages of the differentiation with an ATP-based cell viability assay optimized for 3D-tissues. Concentration responses were investigated after acute (72 h) exposure. Moreover, the compound-specific effect of rotenone was investigated by a panel of ER-stress assay, TUNEL assay, immunocytochemistry, electron microscopy, and in 3D-spheroid based neurite outgrowth assay. The acute exposure to different classes of toxicants revealed distinct susceptibility profiles in a differentiation stage-dependent manner, indicating that hiPSC-based 3D in vitro neurosphere models could be used effectively to evaluate NT, and can be developed further to detect developmental neurotoxicity (DNT) and thus replace or complement the use of animal models in various basic research and pharmaceutical applications. View Full-Text
Keywords: induced pluripotent stem cells; neurospheres; 3D culture; neurite outgrowth; neurotoxicity induced pluripotent stem cells; neurospheres; 3D culture; neurite outgrowth; neurotoxicity
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MDPI and ACS Style

Kobolak, J.; Teglasi, A.; Bellak, T.; Janstova, Z.; Molnar, K.; Zana, M.; Bock, I.; Laszlo, L.; Dinnyes, A. Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening. Cells 2020, 9, 1122. https://doi.org/10.3390/cells9051122

AMA Style

Kobolak J, Teglasi A, Bellak T, Janstova Z, Molnar K, Zana M, Bock I, Laszlo L, Dinnyes A. Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening. Cells. 2020; 9(5):1122. https://doi.org/10.3390/cells9051122

Chicago/Turabian Style

Kobolak, Julianna, Annamaria Teglasi, Tamas Bellak, Zofia Janstova, Kinga Molnar, Melinda Zana, Istvan Bock, Lajos Laszlo, and Andras Dinnyes. 2020. "Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening" Cells 9, no. 5: 1122. https://doi.org/10.3390/cells9051122

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