Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-B pathway inhibition

0517525 - ÚEM 2020 RIV GB eng J - Journal Article
Kárová, Kristýna - Wainwright, J.V. - Machová-Urdzíková, Lucia - Pisal, Rishikaysh - Schmidt, M. - Jendelová, Pavla - Jhanwar-Uniyal, M.
Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-B pathway inhibition.
Journal of Neuroinflammation. Roč. 16, jan. (2019), č. článku 12. E-ISSN 1742-2094
R&D Projects: GA MŠMT(CZ) LTAUSA17120; GA MŠMT(CZ) EF15_003/0000419; GA ČR(CZ) GBP304/12/G069
Institutional support: RVO:68378041
Keywords : NF-B * p65 * spinal cord injury
OECD category: Neurosciences (including psychophysiology
Impact factor: 5.793, year: 2019
Method of publishing: Open access
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1394-7

BackgroundTraumatic spinal cord injury (SCI) triggers a chain of events that is accompanied by an inflammatory reaction leading to necrotic cell death at the core of the injury site, which is restricted by astrogliosis and apoptotic cell death in the surrounding areas. Activation of nuclear factor-B (NF-B) signaling pathway has been shown to be associated with inflammatory response induced by SCI. Here, we elucidate the pattern of activation of NF-B in the pathology of SCI in rats and investigate the effect of transplantation of spinal neural precursors (SPC-01) on its activity and related astrogliosis.MethodsUsing a rat compression model of SCI, we transplanted SPC-01 cells or injected saline into the lesion 7days after SCI induction. Paraffin-embedded sections were used to assess p65 NF-B nuclear translocation at days 1, 3, 7, 10, 14, and 28 and to determine levels of glial scaring, white and gray matter preservation, and cavity size at day 28 after SCI. Additionally, levels of p65 phosphorylated at Serine536 were determined 10, 14, and 28days after SCI as well as levels of locally secreted TNF-.ResultsWe determined a bimodal activation pattern of canonical p65 NF-B signaling pathway in the pathology of SCI with peaks at 3 and 28days after injury induction. Transplantation of SCI-01 cells resulted in significant downregulation of TNF- production at 10 and 14days after SCI and in strong inhibition of p65 NF-B activity at 28days after SCI, mainly in the gray matter. Moreover, reduced formation of glial scar was found in SPC-01-transplanted rats along with enhanced gray matter preservation and reduced cavity size.ConclusionsThe results of this study demonstrate strong immunomodulatory properties of SPC-01 cells based on inhibition of a major signaling pathway. Canonical NF-B pathway activation underlines much of the immune response after SCI including cytokine, chemokine, and apoptosis-related factor production as well as immune cell activation and infiltration. Reduced inflammation may have led to observed tissue sparing. Additionally, such immune response modulation could have impacted astrocyte activation resulting in a reduced glial scar.
Permanent Link: http://hdl.handle.net/11104/0302861