Post-stroke transplantation of adult subventricular zone derived neural progenitor cells - A comprehensive analysis of cell delivery routes and their underlying mechanisms

dc.authorid0000-0001-6494-8923
dc.contributor.authorDoeppner, Thorsten Roland
dc.contributor.authorKaltwasser, Britta
dc.contributor.authorTeli, Mahesh
dc.contributor.authorSánchez-Mendoza, Eduardo
dc.contributor.authorKılıç, Ertuğrul
dc.contributor.authorBaehr, Mathias
dc.contributor.authorHermann, Dirk Matthias
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:55:59Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:55:59Z
dc.date.issued2015
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.descriptionWOS: 000365151800005
dc.descriptionPubMed ID: 26253224
dc.description.abstractWith neuroprotective approaches having failed until recently, current focus on experimental stroke research has switched towards manipulation of post-ischemic neuroregeneration. Transplantation of subventricular zone (SVZ) derived neural progenitor cells (NPCs) is a promising strategy for promotion of neurological recovery. Yet, fundamental questions including the optimal cell delivery route still have to be addressed. Consequently, male C57BL6 mice were exposed to transient focal cerebral ischemia and allowed to survive for as long as 84 days post-stroke. At 6 h post-stroke, NPCs were grafted using six different cell delivery routes, i.e., intravenous, intraarterial, ipsilateral intrastriatal, contralateral intrastriatal, ipsilateral intraventricular and ipsilateral intracortical injection. Control mice received PBS only using the aforementioned delivery routes. Intralesional numbers of GFP(+) NPCs were high only after ipsilateral intrastriatal transplantation, whereas other injection paradigms only yielded comparatively small numbers of grafted cells. However, acute neuroprotection and improved functional outcome were observed after both systemic (i.e., intraarterial and intravenous) and ipsilateral intrastriatal transplantation only. Whereas systemic cell delivery induced acute and long-term neuroprotection, reduction of brain injury after ipsilateral intrastriatal cell grafting was only temporary, in line with the loss of transplanted NPCs in the brain. Both systemic and ipsilateral intrastriatal NPC delivery reduced microglial activation and leukocyte invasion, thus reducing free radical formation within the ischemic brain. On the contrary, only systemic NPC administration stabilized the blood-brain-barrier and reduced leukocytosis in the blood. Although intraarterial NPC transplantation was as effective as intravenous cell grafting, mortality of stroke mice was high using the intraarterial delivery route. Consequently, intravenous delivery of native NPCs in our experimental model is an attractive and effective strategy for stroke therapy that deserves further proof-of-concept studies.
dc.description.sponsorshipTUBITAK [2221]; German Research Council [HE3173/2-2, HE3173/3-1]en_US
dc.description.sponsorshipThe present study was supported by TUBITAK (grant 2221; to TRD) and the German Research Council (HE3173/2-2 and HE3173/3-1; to DMH).en_US
dc.identifier.citationDoeppner, T. R., Kaltwasser, B., Teli, M., Sánchez-Mendoza, E., Kılıç, E., Baehr, M. ... Hermann, D. M. (2015). Post-stroke transplantation of adult subventricular zone derived neural progenitor cells - A comprehensive analysis of cell delivery routes and their underlying mechanisms. Experimental Neurology, 273, 45-56. https://dx.doi.org/10.1016/j.expneurol.2015.07.023
dc.identifier.doi10.1016/j.expneurol.2015.07.023
dc.identifier.endpage56
dc.identifier.issn0014-4886
dc.identifier.issn1090-2430
dc.identifier.scopusqualityQ1
dc.identifier.startpage45
dc.identifier.urihttps://dx.doi.org/10.1016/j.expneurol.2015.07.023
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2511
dc.identifier.volume273
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press
dc.relation.ecinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/2221
dc.relation.ispartofExperimental Neurologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectCerebral Ischemia
dc.subjectStroke
dc.subjectNeural Progenitor Cells
dc.subjectTransplantation
dc.subjectAngioneurogenesis
dc.subjectNeurological Recovery
dc.subjectNeuroregeneration Cell Delivery Routes
dc.subjectNeuroprotection
dc.titlePost-stroke transplantation of adult subventricular zone derived neural progenitor cells - A comprehensive analysis of cell delivery routes and their underlying mechanisms
dc.typeArticle

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