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Neural crest stem c...
Neural crest stem cells protect spinal cord neurons from excitotoxic damage and inhibit glial activation by secretion of brain-derived neurotrophic factor
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- Schizas, Nikos, 1979- (author)
- Uppsala universitet,Ortopedi
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- König, Niclas, 1986- (author)
- Uppsala universitet,Institutionen för neurovetenskap
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- Andersson, Brittmarie (author)
- Uppsala universitet,Ortopedi
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- Vasylovska, Svitlana (author)
- Uppsala universitet,Institutionen för neurovetenskap
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- Hoeber, Jan, 1986- (author)
- Uppsala universitet,Institutionen för neurovetenskap
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- Kozlova, Elena (author)
- Uppsala universitet,Regenerativ neurobiologi
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- Hailer, Nils (author)
- Uppsala universitet,Ortopedi
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(creator_code:org_t)
- 2018-03-07
- 2018
- English.
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In: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 372:3, s. 493-505
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Abstract
Subject headings
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- The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to N-methyl-d-aspartate (NMDA)-induced injury. Immunohistochemistry and TUNEL staining were used to quantitatively study cell populations and apoptosis. Concentrations of neurotrophic factors were measured by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of NeuN-positive neurons that was otherwise observed after NMDA-induced excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced activation of both microglial cells and astrocytes. The concentration of brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects of NCSC application on SCSCs. NCSCs migrated superficially across the surface of SCSCs and showed no signs of neuronal or glial differentiation but preserved their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord tissue, some of these effects mediated by secretion of BDNF. However, the investigated NCSCs seem not to undergo neuronal or glial differentiation in the short term since markers indicative of an undifferentiated state were expressed during the entire observation period.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Neuroprotection
- Suppressed glial activation
- Excitotoxicity
- Apoptosis
- Secretion of soluble factors
Publication and Content Type
- ref (subject category)
- art (subject category)
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Schizas, Nikos, ...
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König, Niclas, 1 ...
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Andersson, Britt ...
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Vasylovska, Svit ...
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Hoeber, Jan, 198 ...
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Kozlova, Elena
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Hailer, Nils
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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Cell and Tissue ...
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Uppsala University