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 H Yolken, James McNulty, Paul Kinchington, David Bloom, Vishwajit Nimgaonkar

Research output: Contribution to journalArticle

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

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Central Nervous System Viral Diseases
Induced Pluripotent Stem Cells
Preclinical Drug Evaluations
Acyclovir
Neurology
Screening
Central Nervous System
Viruses
Central Nervous System Infections
Human Herpesvirus 1
Virus Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurodegenerative diseases
Inhibitory Concentration 50
Flow Cytometry
Flow cytometry
Pathogens
Stem cells
Scaffolds

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

Cite this

D'Aiuto, L., Naciri, J., Radio, N., Tekur, S., Clayton, D., Apodaca, G., ... Nimgaonkar, V. (2018). Generation of three-dimensional human neuronal cultures: Application to modeling CNS viral infections. Stem Cell Research and Therapy, 9(1), [134]. https://doi.org/10.1186/s13287-018-0881-6

Generation of three-dimensional human neuronal cultures : Application to modeling CNS viral infections. / D'Aiuto, Leonardo; Naciri, Jennifer; Radio, Nicholas; Tekur, Sesha; Clayton, Dennis; Apodaca, Gerard; Di Maio, Roberto; Zhi, Yun; Dimitrion, Peter; Piazza, Paolo; Demers, Matthew; Wood, Joel; Chu, Charleen; Callio, Jason; McClain, Lora; Yolken, Robert H; McNulty, James; Kinchington, Paul; Bloom, David; Nimgaonkar, Vishwajit.

In: Stem Cell Research and Therapy, Vol. 9, No. 1, 134, 11.05.2018.

Research output: Contribution to journalArticle

D'Aiuto, L, Naciri, J, Radio, N, Tekur, S, Clayton, D, Apodaca, G, Di Maio, R, Zhi, Y, Dimitrion, P, Piazza, P, Demers, M, Wood, J, Chu, C, Callio, J, McClain, L, Yolken, RH, McNulty, J, Kinchington, P, Bloom, D & Nimgaonkar, V 2018, 'Generation of three-dimensional human neuronal cultures: Application to modeling CNS viral infections', Stem Cell Research and Therapy, vol. 9, no. 1, 134. https://doi.org/10.1186/s13287-018-0881-6
D'Aiuto, Leonardo ; Naciri, Jennifer ; Radio, Nicholas ; Tekur, Sesha ; Clayton, Dennis ; Apodaca, Gerard ; Di Maio, Roberto ; Zhi, Yun ; Dimitrion, Peter ; Piazza, Paolo ; Demers, Matthew ; Wood, Joel ; Chu, Charleen ; Callio, Jason ; McClain, Lora ; Yolken, Robert H ; McNulty, James ; Kinchington, Paul ; Bloom, David ; Nimgaonkar, Vishwajit. / Generation of three-dimensional human neuronal cultures : Application to modeling CNS viral infections. In: Stem Cell Research and Therapy. 2018 ; Vol. 9, No. 1.
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AU - Radio, Nicholas

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AU - Clayton, Dennis

AU - Apodaca, Gerard

AU - Di Maio, Roberto

AU - Zhi, Yun

AU - Dimitrion, Peter

AU - Piazza, Paolo

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AU - Wood, Joel

AU - Chu, Charleen

AU - Callio, Jason

AU - McClain, Lora

AU - Yolken, Robert H

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AU - Bloom, David

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