Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell ther
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RESEARCH
Open Access
Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy Chenhong Lin1†, Cinzia Calzarossa1,2†, Teresa Fernandez-Zafra3, Jia Liu1,4, Xiaofei Li1, Åsa Ekblad-Nordberg5, Erika Vazquez-Juarez1, Simone Codeluppi3, Lena Holmberg1, Maria Lindskog1, Per Uhlén3 and Elisabet Åkesson1,6*
Abstract Background: There 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. Methods: We 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. Results: The 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. Conclusions: We conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies. Keywords: Spinal cord injury, Stem cell therapy, Human organotypic culture
Background Human central nervous system (CNS) lesions, such as spinal cord injury (SCI), present limited spontaneous regenerative properties and largely lack available treatments offering functional improvement. Numerous and * Correspondence: [email protected] † Chenhong Lin and Cinzia Calzarossa shared first authorship. 1 Department of Neurobiology, Care Sciences and Society, Div. of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden 6 The R&D Unit, Stockholms Sjukhem, Stockholm, Sweden Full list of author information is available at the end of the article
often promising pre-clinical studies with various neuroprotective compounds, factors supporting regeneration as well as cell therapies have led to multiple clinical trials [1–4]. However, translation from experimental animal models to the clinical settings has proven to be challenging. State-of-the-art treatment for traumatic SCI aims to limit the lesion to a m
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