Functional and Mechanistic Neurotoxicity Profiling Using Human iPSC-Derived Neural 3D Cultures

Toxicological Sciences : an Official Journal of the Society of Toxicology
Oksana SirenkoCassiano Carromeu

Abstract

Neurological disorders affect millions of people worldwide and appear to be on the rise. Whereas the reason for this increase remains unknown, environmental factors are a suspected contributor. Hence, there is an urgent need to develop more complex, biologically relevant, and predictive in vitro assays to screen larger sets of compounds with the potential for neurotoxicity. Here, we employed a human induced pluripotent stem cell (iPSC)-based 3D neural platform composed of mature cortical neurons and astrocytes as a model for this purpose. The iPSC-derived human 3D cortical neuron/astrocyte co-cultures (3D neural cultures) present spontaneous synchronized, readily detectable calcium oscillations. This advanced neural platform was optimized for high-throughput screening in 384-well plates and displays highly consistent, functional performance across different wells and plates. Characterization of oscillation profiles in 3D neural cultures was performed through multi-parametric analysis that included the calcium oscillation rate and peak width, amplitude, and waveform irregularities. Cellular and mitochondrial toxicity were assessed by high-content imaging. For assay characterization, we used a set of neuromodulators with known me...Continue Reading

References

Oct 1, 1976·Environmental Health Perspectives·C C Lee, P J Peters
Jan 1, 1992·American Journal of Industrial Medicine·J D KaufmanL Rosenstock
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J E Huettner, B P Bean
Oct 1, 1988·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N OgataT Narahashi
Sep 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·E H WongL L Iversen
Jan 1, 1993·Archives of Insect Biochemistry and Physiology·J E Casida
Jan 1, 1996·Annual Review of Entomology·J R Bloomquist
Jul 1, 1996·Pharmacology & Toxicology·T Narahashi
Nov 21, 1997·Brain Research·X Wang, E I Gruenstein
Jun 5, 1999·Methods : a Companion to Methods in Enzymology·D SmettersR Yuste
Dec 2, 2000·Nature Neuroscience·E C BeattieR C Malenka
Feb 15, 2001·European Journal of Pharmacology·C MartínezM J García de Boto
May 2, 2001·Nature Reviews. Neuroscience·R C CarrollR C Malenka
Jun 22, 2001·Neurotoxicology and Teratology·C V VorheesD R Minck
Nov 8, 2001·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·E F Wijdicks
Jan 29, 2002·Toxicology·David M SoderlundMyra L Weiner
Feb 5, 2003·The Journal of General Physiology·Michael F Sheets, Dorothy A Hanck
Jun 27, 2003·Journal of Toxicology and Environmental Health. Part a·Y TangM M Mumtaz
Sep 10, 2003·Drugs·David R GoldsmithCaroline M Perry
Mar 25, 2004·Trends in Biotechnology·Jens M Kelm, Martin Fussenegger
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
Apr 2, 2004·Nature·Robert Langer, David A Tirrell
Jun 12, 2004·Journal of Biomolecular Screening·Leoni A Kunz-SchughartReinhard Ebner
Jul 21, 2004·Archives of Environmental Health·Mohamed B Abou-Donia
Oct 14, 2005·Epidemiology·Igor BurstynPaolo Boffetta
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ali KhademhosseiniJoseph P Vacanti
May 12, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sonya M BilliardRichard T Di Giulio
Jun 15, 2007·Neurochemistry International·Leanne CoyneRobert F Halliwell
Jul 8, 2008·Brain Research·Eyal CohenMenahem Segal
Oct 24, 2008·Environmental Health : a Global Access Science Source·Marina Bjørling-PoulsenPhilippe Grandjean

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Citations

Jun 13, 2020·Critical Reviews in Toxicology·Deepika DeepikaVikas Kumar
Nov 5, 2019·Frontiers in Cellular Neuroscience·Matthew V GreenStanley A Thayer
Apr 24, 2020·Current Pharmaceutical Biotechnology·Toshikatsu MatsuiTadahiro Shinozawa
Dec 4, 2020·Archives of Toxicology·Dominik LoserUdo Kraushaar
Feb 4, 2021·International Journal of Molecular Sciences·Lu Qian, Julia Tcw
Jan 28, 2021·EMBO Molecular Medicine·Cleber A TrujilloAlysson R Muotri
Oct 31, 2020·Trends in Molecular Medicine·Svetlana Pasteuning-VuhmanR Jeroen Pasterkamp
May 30, 2020·Trends in Molecular Medicine·Daniele ZinkJackie Y Ying
Feb 26, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Sara WellensMaxime Culot
Mar 7, 2021·International Journal of Molecular Sciences·Ileana SlavinCassiano Carromeu
Dec 24, 2020·Small·Ellen FritscheKatharina Koch
Apr 24, 2021·Molecular Psychiatry·Priscilla D NegraesAlysson R Muotri
Jul 13, 2021·Frontiers in Molecular Biosciences·Kseniia Sarieva, Simone Mayer
Aug 3, 2021·Frontiers in Molecular Neuroscience·Henrik RennerJan M Bruder
Oct 2, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Aleksandr Shcheglovitov, Randall T Peterson
Nov 9, 2021·Disease Models & Mechanisms·Aaron R ShoemakerJohn D Finan

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