Neural Crest Stem Cells protect Spinal Cord Slice Cultures from Excitotoxic Neuronal Damage and Inhibit Glial Activation
(English)Manuscript (preprint) (Other academic)
Neural Crest Stem Cells (NCSC) possess anti-inflammatory properties and they could therefore have protective effects on neurons after spinal cord injury (SCI). We investigated if NCSCs reduce neuronal loss and glial activation after excitotoxic injury in spinal cord slice cultures (SCSCs). SCSCs subjected to N-Methyl-D-Aspartate (NMDA)-induced injury were either treated by transplantation of NCSC or with interleukin-1 receptor antagonist (IL1RA). Immunohistochemistry for Neuronal Nuclei (NeuN), glial fibrillary acidic protein (GFAP) and MacII were used to study neuronal and glial populations, and TUNEL staining to visualize apoptotic cells. Migration and differentiation of NCSCs on SCSCs, laminin or a hyaluronic acid hydrogel were investigated by immunohistochemistry. NCSCs counteracted the neuronal loss observed after NMDA-induced excitotoxicity and reduced the proportion of apoptotic cells. Transplantation of NCSCs also reduced the number of activated microglial cells in the white matter and the number of activated astrocytes in the grey matter of NMDA-injured SCSCs. The majority of NCSCs migrated superficially across the surface of SCSCs with some of them penetrating into the tissue. NCSCs did not show signs of neuronal or glial differentiation, however, the markers SOX2 and Krox20 were expressed which indicated an undifferentiated state of NCSCs. In conclusion, NCSCs have neuroprotective, anti-apoptotic and anti-inflammatory effects on SCSCs subjected to excitotoxicity, similar to the effects of IL1RA. Since the majority of NCSCs did not migrate through SCSCs they are likely to exert their actions through the secretion of soluble factors.
Neuroprotection, Suppressed glial activation, excitotoxicity, apoptosis
Medical and Health Sciences
Research subject Medical Science
IdentifiersURN: urn:nbn:se:uu:diva-251476OAI: oai:DiVA.org:uu-251476DiVA: diva2:806231