Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy
| Autor: | Teresa Fernandez-Zafra, Åsa Ekblad-Nordberg, Elisabet Åkesson, Xiaofei Li, Simone Codeluppi, Erika Vázquez-Juárez, Jia Liu, Lena Holmberg, Per Uhlén, Maria Lindskog, Cinzia Calzarossa, Chenhong Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.medical_treatment Central nervous system Population Medicine (miscellaneous) Spinal cord injury Biochemistry Genetics and Molecular Biology (miscellaneous) lcsh:Biochemistry Human organotypic culture medicine lcsh:QD415-436 education education.field_of_study lcsh:R5-920 Stem cell therapy business.industry Research Cell Biology Stem-cell therapy medicine.disease Spinal cord medicine.anatomical_structure Molecular Medicine Stem cell business lcsh:Medicine (General) Neural development Ex vivo |
| Zdroj: | Stem Cell Research & Therapy Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-18 (2020) |
| ISSN: | 1757-6512 |
| Popis: | BackgroundThere are multiple promising treatment strategies for central nervous system trauma and disease. However, to develop clinically potent and safe treatments, models of human-specific conditions are needed to complement in vitro and in vivo animal model-based studies.MethodsWe established human brain stem and spinal cord (cross- and longitudinal sections) organotypic cultures (hOCs) from first trimester tissues after informed consent by donor and ethical approval by the Regional Human Ethics Committee, Stockholm (lately referred to as Swedish Ethical Review Authority), and The National Board of Health and Welfare, Sweden. We evaluated the stability of hOCs with a semi-quantitative hOC score, immunohistochemistry, flow cytometry, Ca2+signaling, and electrophysiological analysis. We also applied experimental allogeneic human neural cell therapy after injury in the ex vivo spinal cord slices.ResultsThe spinal cord hOCs presented relatively stable features during 7–21 days in vitro (DIV) (except a slightly increased cell proliferation and activated glial response). After contusion injury performed at 7 DIV, a significant reduction of the hOC score, increase of the activated caspase-3+cell population, and activated microglial populations at 14 days postinjury compared to sham controls were observed. Such elevation in the activated caspase-3+population and activated microglial population was not observed after allogeneic human neural cell therapy.ConclusionsWe conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies. |
| Databáze: | OpenAIRE |
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