An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue

Fernández-Zafra, Teresa; Codeluppi, Simone; Uhlén, Per

doi:10.1016/j.yexcr.2017.06.002

Cited by 13 publications

(11 citation statements)

References 40 publications

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“…This may be due to both the denervation at slice preparation and proliferation and cellular migration in the developing spinal cord. Fernandez-Zafra et al, albeit to a lesser degree, reported a similar finding with proliferation in the neuroepithelial cell layers with subsequent migration in adult rodent spinal cord slice cultures [23].…”

Section: Discussionmentioning

confidence: 70%

“…One ex vivo human spinal cord schwannoma culture [ 45 ], one postmortem human spinal cord model derived from adult autopsy tissue [ 46 ], and one human fetal spinal cord tissue culture [ 47 ]. However, different from these previous reports, the human slice culture method utilized in the present study is an interface-based method (modified from the method by Stoppini et al [ 13 ] and Bonnici and Kapfhammer [ 48 ]) that retained relatively intact anatomical structure, local circuitry, glial/neuronal interactions, and viability similar to that reported in cultures of rodent origin [ 23 , 49 – 51 ].…”

Section: Discussionmentioning

confidence: 93%

“…So far, CNS slice culture with tissue from embryonic, postnatal, and adult stages has mainly been utilized in rodents. Both cross-sectional and longitudinal organotypic slice cultures from animal spinal cord have been developed [21][22][23][24][25][26] and used to study SCI [27][28][29] and cell therapy [17][18][19][20]. However, to develop treatment strategies for human SCI, studies of species-specific anatomical, physiological, and immunological features [30][31][32] are central [33,34] and should be further utilized.…”

Section: Introductionmentioning

confidence: 99%

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Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

et al. 2020

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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, Ca 2+ 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.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

et al. 2020

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“…However, there are limitations in the slice culture model as there is no circulating blood and therefore a limited ability to examine immune responses. The accumulation of microglia/macrophages occurs at the edges of slices due to damage caused by the dissection and tissue chopping procedures (Fernandez-Zafra et al, 2017). We optimised our culture protocol by delaying any treatment until day 4 to avoid immune cell involvement from the tissue harvest procedure.…”

Section: Discussionmentioning

confidence: 99%

Analysis of reactive astrocytes and NG2 proteoglycan in ex vivo rat models of spinal cord injury

Patar

Dockery

Howard

et al. 2019

Journal of Neuroscience Methods

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“…For spinal cord organotypic slices, the protocol described in (Fernandez-Zafra, Codeluppi, et Uhlén 2017) was used except that glutamine (2 mM final concentration) was used instead of glutamax and poly-D-lysine instead of poly-L-lysine for coating. Slices (300 µm) were fixed with paraformaldehyde (4%, 20 min, room temperature) directly after sectioning (t=0) or after 72 h in culture.…”

Section: Cell Culturesmentioning

confidence: 99%

Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells

Chevreau

Ghazale

Ripoll

et al. 2021

Preprint

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Ependymal cells reside in the adult spinal cord around the central canal and have stem cell properties in vitro. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying their activation and their glial-biased differentiation in mammals remain ill-defined. This represents an obstacle to control these cells. We addressed this issue using RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling during injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, six of them more than 20 fold, namely Crym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr. OSMR is the receptor for the inflammatory cytokine oncostatin (OSM) and we studied its regulation and role using neurospheres derived from ependymal cells. We found that OSM induces strong OSMR and p-STAT3 expression together with proliferation reduction and astrocytic differentiation. Conversely, production of oligodendrocyte-lineage OLIG1+ cells was reduced. OSM is specifically expressed by microglial cells and was strongly upregulated after injury. We observed microglial cells apposed to ependymal cells in vivo and co-cultures experiments showed that these cells upregulate OSMR in neurosphere cells. Collectively, these results support the notion that microglial cells and OSMR/OSM pathway regulate ependymal cells in injury. In addition, the generated high throughput data provides a unique molecular resource to study how ependymal cell react to spinal cord lesion.

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An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue

Cited by 13 publications

References 40 publications

Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy

Analysis of reactive astrocytes and NG2 proteoglycan in ex vivo rat models of spinal cord injury

Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells

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