Journal
STEM CELL RESEARCH & THERAPY
Volume 9, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13287-018-0881-6
Keywords
Human induced pluripotent stem cells (hiPSCs); Three-dimensional (3D) neuronal cultures; Antiviral drug screening; Herpes simplex virus type 1 (HSV-1); High content screening; Neurodegeneration; CX7 High-Content Screening (HCS) Platform
Funding
- NIH [R21 NS096405-01A1, MH63480, R01 AG026389]
- Stanley Medical Research Institute [07R-1712]
- Pittsburgh Center for Kidney Research Kidney Imaging Core NIH [P30 DK079307]
- Michael J. Fox Foundation for Parkinson's Research
- 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
- Golub Capital
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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 mu M and 3.12 mu M 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.
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