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dc.contributor.authorBernstock, Joshuaen
dc.contributor.authorPeruzzotti Jametti, Lucaen
dc.contributor.authorLeonardi, Tommasoen
dc.contributor.authorVicario, Nunzioen
dc.contributor.authorYe, Danielen
dc.contributor.authorLee, Yang-Jaen
dc.contributor.authorMaric, Draganen
dc.contributor.authorJohnson, Kory Ren
dc.contributor.authorMou, Yongshanen
dc.contributor.authorVan Den Bosch, Alettaen
dc.contributor.authorWinterbone, Marken
dc.contributor.authorFriedman, Gregory Ken
dc.contributor.authorFranklin, Robinen
dc.contributor.authorHallenbeck, John Men
dc.contributor.authorPluchino, Stefanoen
dc.date.accessioned2019-03-26T00:30:29Z
dc.date.available2019-03-26T00:30:29Z
dc.date.issued2019-04en
dc.identifier.issn2352-3964
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290829
dc.description.abstractBackground: Neural stem cell (NSC)-based therapies hold great promise for treating diseases of the central nervous system (CNS). However, several fundamental problems still need to be overcome to fully exploit the clinical potential of NSC therapeutics. Chief among them is the limited survival of NSC grafts within hostile microenvironments. Methods: Herein, we sought to engineer NSCs in an effort to increase graft survival within ischemic brain lesions via upregulation of global SUMOylation, a post-translational modification critically involved in mediating tolerance to ischemia/reperfusion. Findings: NSCs overexpressing the SUMO E2-conjugase Ubc9 displayed resistance to oxygen-glucose-deprivation/restoration of oxygen/glucose (OGD/ROG) and enhanced neuronal differentiation in vitro, as well as increased survival and neuronal differentiation when transplanted in mice with transient middle cerebral artery occlusion in vivo. Interpretation: Our work highlights a critical role for SUMOylation in NSC biology and identifies a biological pathway that can be targeted to increase the effectiveness of exogenous stem cell medicines in ischemic stroke. Fund: Intramural Research Program of the NINDS/NIH, the Italian Multiple Sclerosis Foundation (FISM), the Bascule Charitable Trust, NIH-IRTA-OxCam and Wellcome Trust Research Training Fellowships.
dc.description.sponsorshipIntramural Research Program of the NINDS/NIH The Italian Multiple Sclerosis Foundation (FISM) The Bascule Charitable Trust NIH-IRTA-OxCam Wellcome Trust Research Training Fellowships
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rights
dc.rights.uri
dc.subjectNeuronsen
dc.subjectAnimalsen
dc.subjectMice, Transgenicen
dc.subjectMiceen
dc.subjectOxygenen
dc.subjectUbiquitin-Conjugating Enzymesen
dc.subjectGlucoseen
dc.subjectStem Cell Transplantationen
dc.subjectGene Expression Profilingen
dc.subjectComputational Biologyen
dc.subjectSignal Transductionen
dc.subjectCell Cycleen
dc.subjectCell Survivalen
dc.subjectGene Expressionen
dc.subjectEnergy Metabolismen
dc.subjectMaleen
dc.subjectStrokeen
dc.subjectNeurogenesisen
dc.subjectSumoylationen
dc.subjectNeural Stem Cellsen
dc.subjectBiomarkersen
dc.titleSUMOylation promotes survival and integration of neural stem cell grafts in ischemic stroke.en
dc.typeArticle
prism.endingPage224
prism.publicationDate2019en
prism.publicationNameEBioMedicineen
prism.startingPage214
prism.volume42en
dc.identifier.doi10.17863/CAM.38020
dcterms.dateAccepted2019-03-13en
rioxxterms.versionofrecord10.1016/j.ebiom.2019.03.035en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-04en
dc.contributor.orcidBernstock, Joshua [0000-0002-7814-3867]
dc.contributor.orcidPeruzzotti-Jametti, Luca [0000-0002-9396-5607]
dc.contributor.orcidLeonardi, Tommaso [0000-0002-4449-1863]
dc.contributor.orcidVicario, Nunzio [0000-0001-5934-3962]
dc.contributor.orcidFriedman, Gregory K [0000-0002-6653-7420]
dc.contributor.orcidFranklin, Robin [0000-0001-6522-2104]
dc.contributor.orcidPluchino, Stefano [0000-0002-6267-9472]
dc.identifier.eissn2352-3964
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBascule Charitable Trust (RG75149)
pubs.funder-project-idWellcome Trust (105795/Z/14/Z)
pubs.funder-project-idWELLCOME TRUST (105795/Z/14/Z)
pubs.funder-project-idMRC (MC_PC_12009)
rioxxterms.freetoread.startdate2022-03-25


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