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dc.contributor.authorJohnson, William Eustace Basil
dc.contributor.authorWatanabe, Shuji
dc.contributor.authorUchida, Kenzo
dc.contributor.authorNakajima, Hideaki
dc.contributor.authorMatsuo, Hideaki
dc.contributor.authorSugita, Daisuke
dc.contributor.authorYoshida, Ai
dc.contributor.authorHonjoh, Kazuya
dc.contributor.authorBaba, Hisatoshi
dc.date.accessioned2020-06-26T09:53:38Z
dc.date.available2020-06-26T09:53:38Z
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/623523/stem.2006.pdf?sequence=3
dc.identifier.citationWatanabe, S., Uchida, K., Nakajima, H., Matsuo, H., Sugita, D., Yoshida, A., . . . Baba, H. (2015). Early transplantation of mesenchymal stem cells after spinal cord injury relieves pain hypersensitivity through suppression of pain-related signaling cascades and reduced inflammatory cell recruitment. Stem Cells, 33(6), 1902-1914en_US
dc.identifier.urihttp://hdl.handle.net/10034/623523
dc.descriptionThis novel study demonstrated that mesenchymal stem cell transplants after spinal cord injury reduce neuropathic pain, giving details of reduced pain signalling pathways affected. The work is essential in the translation of stem cell therapies for CNS regeneration.en_US
dc.description.abstractBone marrow-derived mesenchymal stem cells (BMSC) modulate inflammatory/immune responses and promote motor functional recovery after spinal cord injury (SCI). However, the effects of BMSC transplantation on central neuropathic pain and neuronal hyperexcitability after SCI remain elusive. This is of importance because BMSC-based therapies have been proposed for clinical treatment. We investigated the effects of BMSC transplantation on pain hypersensitivity in green fluorescent protein (GFP)-positive bone marrow-chimeric mice subjected to a contusion SCI, and the mechanisms of such effects. BMSC transplantation at day 3 post-SCI improved motor function and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. The pain improvements were mediated by suppression of protein kinase C-γ and phosphocyclic AMP response element binding protein expression in dorsal horn neurons. BMSC transplants significantly reduced levels of p-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (p-ERK1/2) in both hematogenous macrophages and resident microglia and significantly reduced the infiltration of CD11b and GFP double-positive hematogenous macrophages without decreasing the CD11b-positive and GFP-negative activated spinal-microglia population. BMSC transplants prevented hematogenous macrophages recruitment by restoration of the blood-spinal cord barrier (BSCB), which was associated with decreased levels of (a) inflammatory cytokines (tumor necrosis factor-α, interleukin-6); (b) mediators of early secondary vascular pathogenesis (matrix metallopeptidase 9); (c) macrophage recruiting factors (CCL2, CCL5, and CXCL10), but increased levels of a microglial stimulating factor (granulocyte-macrophage colony-stimulating factor). These findings support the use of BMSC transplants for SCI treatment. Furthermore, they suggest that BMSC reduce neuropathic pain through a variety of related mechanisms that include neuronal sparing and restoration of the disturbed BSCB, mediated through modulation of the activity of spinal-resident microglia and the activity and recruitment of hematogenous macrophages.en_US
dc.publisherAlphaMed Press/Wileyen_US
dc.relation.urlhttps://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.2006en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectStem cellsen_US
dc.subjectspinal cord injuryen_US
dc.subjectregenerative medicineen_US
dc.titleEarly Transplantation of Mesenchymal Stem Cells After Spinal Cord Injury Relieves Pain Hypersensitivity Through Suppression of Pain-Related Signaling Cascades and Reduced Inflammatory Cell Recruitmenten_US
dc.typeArticleen_US
dc.identifier.eissn1549-4918en_US
dc.contributor.departmentAston University, University of Fukuien_US
dc.identifier.journalStem Cellsen_US
or.grant.openaccessYesen_US
rioxxterms.funderJapanen_US
rioxxterms.identifier.projectUnfundeden_US
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1002/stem.2006en_US
rioxxterms.licenseref.startdate2015-03-24
refterms.dateFCD2020-06-23T14:36:01Z
refterms.versionFCDAM
refterms.dateFOA2020-06-26T09:53:39Z
rioxxterms.publicationdate2015-03-24
dc.dateAccepted2015-03-11
dc.date.deposited2020-06-26en_US
dc.indentifier.issn1066-5099en_US


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