TY - JOUR
T1 - Generation of three-dimensional human neuronal cultures
T2 - Application to modeling CNS viral infections
AU - D'Aiuto, Leonardo
AU - Naciri, Jennifer
AU - Radio, Nicholas
AU - Tekur, Sesha
AU - Clayton, Dennis
AU - Apodaca, Gerard
AU - Di Maio, Roberto
AU - Zhi, Yun
AU - Dimitrion, Peter
AU - Piazza, Paolo
AU - Demers, Matthew
AU - Wood, Joel
AU - Chu, Charleen
AU - Callio, Jason
AU - McClain, Lora
AU - Yolken, Robert
AU - McNulty, James
AU - Kinchington, Paul
AU - Bloom, David
AU - Nimgaonkar, Vishwajit
N1 - Funding Information:
This work was supported by NIH grants R21 NS096405-01A1, MH63480, and R01 AG026389, the Stanley Medical Research Institute (07R-1712), and the Pittsburgh Center for Kidney Research Kidney Imaging Core NIH P30 DK079307. PPMI, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbvie, Allergan, Avid Radiopharmaceuticals, Biogen, BioLegend, Bristol-Myers Squibb, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Sanofi Genzyme, Servier, Takeda, Teva, Ucb, and Golub Capital. The funding agents had no role in the design of the study, in the collection, analysis and interpretation of data, or in writing the manuscript.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/5/11
Y1 - 2018/5/11
N2 - 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.
AB - 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.
KW - Antiviral drug screening
KW - CX7 High-Content Screening (HCS) Platform
KW - Herpes simplex virus type 1 (HSV-1)
KW - High content screening
KW - Human induced pluripotent stem cells (hiPSCs)
KW - Neurodegeneration
KW - Three-dimensional (3D) neuronal cultures
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U2 - 10.1186/s13287-018-0881-6
DO - 10.1186/s13287-018-0881-6
M3 - Article
C2 - 29751846
AN - SCOPUS:85046949572
SN - 1757-6512
VL - 9
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
IS - 1
M1 - 134
ER -