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

Leonardo D'Aiuto, Jennifer Naciri, Nicholas Radio, Sesha Tekur, Dennis Clayton, Gerard Apodaca, Roberto Di Maio, Yun Zhi, Peter Dimitrion, Paolo Piazza, Matthew Demers, Joel Wood, Charleen Chu, Jason Callio, Lora McClain, Robert Yolken, James McNulty, Paul Kinchington, David Bloom, Vishwajit Nimgaonkar

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: Our A-3D neuronal cultures provide an unprecedented opportunity for high-content drug screening programs to treat human CNS infections.

Original languageEnglish (US)
Article number134
JournalStem Cell Research and Therapy
Volume9
Issue number1
DOIs
StatePublished - May 11 2018

Keywords

  • Antiviral drug screening
  • CX7 High-Content Screening (HCS) Platform
  • Herpes simplex virus type 1 (HSV-1)
  • High content screening
  • Human induced pluripotent stem cells (hiPSCs)
  • Neurodegeneration
  • Three-dimensional (3D) neuronal cultures

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

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