Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections

Stem Cell Research & Therapy
Leonardo D'AiutoVishwajit L Nimgaonkar

Abstract

A variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells (hiPSCs) offer an extraordinary window for modeling pathogen-CNS interactions, and other cellular interactions, in three-dimensional (3D) neuronal cultures that can recapitulate several aspects of in vivo brain tissue. Herein, we describe a prototype of scaffold-free hiPSC-based adherent 3D (A-3D) human neuronal cultures in 96-well plates. To test their suitability for drug screening, A-3D neuronal cultures were infected with herpes simplex virus type 1 (HSV-1) with or without acyclovir. The half maximal inhibitory concentration (IC50) of acyclovir was 3.14 μM and 3.12 μM determined using flow cytometry and the CX7 High Content Screening platform, respectively. Our A-3D neuronal cultures provide an unprecedented opportunity for high-content drug screening programs to treat human CNS infections.

References

Oct 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shulamit LevenbergRobert Langer
Jan 12, 2005·Genome Biology·Leif Dehmelt, Shelley Halpain
Mar 18, 2006·Neuroscience Research·Zoltán Molnár, Amanda F P Cheung
May 24, 2007·Journal of Neuroscience Research·K BrännvallK Forsberg-Nilsson
Aug 22, 2008·Nature·Nicolas GaspardPierre Vanderhaeghen
Oct 5, 2011·Critical Reviews in Biomedical Engineering·D Kacy CullenMichelle C LaPlaca
Jan 19, 2012·Pharmacology & Therapeutics·Anna AstashkinaDavid W Grainger
Jun 5, 2012·Biomaterials·Muhammad F B DaudJohn W Haycock
Jul 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jessica MarianiFlora M Vaccarino
Sep 3, 2013·Nature·Madeline A LancasterJuergen A Knoblich
Oct 1, 2013·Cell·Marina Bershteyn, Arnold R Kriegstein
Feb 1, 2014·Differentiation; Research in Biological Diversity·Osama MohamadLing Wei
Mar 19, 2014·Biomaterials·Angela BozzaSimona Casarosa
May 17, 2014·Assay and Drug Development Technologies·Rasheena EdmondsonLiju Yang
Jan 31, 2015·Oncology Reports·Yoshinori ImamuraHironobu Minami
Jun 17, 2015·Antiviral Research·Lora McClainLeonardo D'Aiuto
Mar 28, 2017·Antiviral Research·Leonardo D'AiutoVishwajit L Nimgaonkar

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Citations

Aug 14, 2020·Biomaterials Science·Vivek Damodar RanjanLi Zeng
Jan 25, 2020·Lab on a Chip·David A SosciaNicholas O Fischer
Oct 7, 2020·Brain : a Journal of Neurology·Polyxeni NikolakopoulouAnna Herland
Oct 19, 2019·Journal of Neuroscience Methods·Doris LamNicholas O Fischer
Apr 10, 2021·APL Bioengineering·Danielle WarrenJeremy M Crook
May 15, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Lisa BelfioreMartin Engel
Oct 31, 2020·European Journal of Pharmacology·Temitope Isaac AdelusiOlamide Tosin Olaoba

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Methods Mentioned

BETA
biopsy
biopsies
flow cytometry
confocal microscopy

Software Mentioned

R
HCS ) Studio
LAS AF
drc
high

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