Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections
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 pathogenes...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0881-6 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Leonardo D’Aiuto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T12:41:51Z |
| format | Article |
| id | doaj.art-9d2ce73530f44a3ca7143eeeee2e5968 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-22T12:41:51Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-9d2ce73530f44a3ca7143eeeee2e59682022-12-21T18:25:25ZengBMCStem Cell Research & Therapy1757-65122018-05-01911910.1186/s13287-018-0881-6Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infectionsLeonardo D’Aiuto0Jennifer Naciri1Nicholas Radio2Sesha Tekur3Dennis Clayton4Gerard Apodaca5Roberto Di Maio6Yun Zhi7Peter Dimitrion8Paolo Piazza9Matthew Demers10Joel Wood11Charleen Chu12Jason Callio13Lora McClain14Robert Yolken15James McNulty16Paul Kinchington17David Bloom18Vishwajit Nimgaonkar19Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and ClinicDepartment of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and ClinicThermo Fisher Scientific, Cellular Imaging and AnalysisThermo Fisher Scientific, Cellular Imaging and AnalysisDepartment of Medicine Renal-Electrolyte Division and Department of Cell Biology, University of Pittsburgh School of MedicineDepartment of Medicine Renal-Electrolyte Division and Department of Cell Biology, University of Pittsburgh School of MedicinePittsburgh Institute for Neurodegenerative Diseases, University of PittsburghDepartment of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua UniversityDivision of Neurovirology, Department of Pediatrics, Johns Hopkins University School of MedicineDepartment of Infectious Diseases and Microbiology, University of PittsburghDepartment of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and ClinicDepartment of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and ClinicPittsburgh Institute for Neurodegenerative Diseases, University of PittsburghDepartment of Pathology, Division of Neuropathology, University of Pittsburgh School of MedicineMagee Women’s Research InstituteDivision of Neurovirology, Department of Pediatrics, Johns Hopkins University School of MedicineDepartment of Chemistry and Chemical-Biology, McMaster UniversityDepartment of Ophthalmology, University of Pittsburgh School of MedicineDepartment of Molecular Genetics & Microbiology, University of Florida College of MedicineDepartment of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and ClinicAbstract 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.http://link.springer.com/article/10.1186/s13287-018-0881-6Human induced pluripotent stem cells (hiPSCs)Three-dimensional (3D) neuronal culturesAntiviral drug screeningHerpes simplex virus type 1 (HSV-1)High content screeningNeurodegeneration |
| spellingShingle | 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 Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections Stem Cell Research & Therapy 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 |
| title | Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections |
| title_full | Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections |
| title_fullStr | Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections |
| title_full_unstemmed | Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections |
| title_short | Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections |
| title_sort | generation of three dimensional human neuronal cultures application to modeling cns viral infections |
| topic | 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 |
| url | http://link.springer.com/article/10.1186/s13287-018-0881-6 |
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