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Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1 alpha/CXC chemokine receptor 4 pathway

DC FieldValueLanguage
dc.contributor.author박국인-
dc.date.accessioned2015-07-14T17:14:02Z-
dc.date.available2015-07-14T17:14:02Z-
dc.date.issued2004-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/112472-
dc.description.abstractMigration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified. Because NSCs seem to home similarly to pathologic sites derived from disparate etiologies, we hypothesized that the inflammatory response itself, a characteristic common to all, guides the behavior of potentially reparative cells. As proof of concept, we show that human NSCs migrate in vivo (including from the contralateral hemisphere) toward an infarcted area (a representative CNS injury), where local astrocytes and endothelium up-regulate the inflammatory chemoattractant stromal cell-derived factor 1α (SDF-1α). NSCs express CXC chemokine receptor 4 (CXCR4), the cognate receptor for SDF-1α. Exposure of SDF-1α to quiescent NSCs enhances proliferation, promotes chain migration and transmigration, and activates intracellular molecular pathways mediating engagement. CXCR4 blockade abrogates their pathology-directed chain migration, a developmentally relevant mode of tangential migration that, if recapitulated, could explain homing along nonstereotypical paths. Our data implicate SDF-1α/CXCR4, representative of the inflammatory milieu characterizing many pathologies, as a pathway that activates NSC molecular programs during injury and suggest that inflammation may be viewed not simply as playing an adverse role but also as providing stimuli that recruit cells with a regenerative homeostasis-promoting capacity. CXCR4 expression within germinal zones suggests that NSC homing after injury and migration during development may invoke similar mechanisms.-
dc.description.statementOfResponsibilityopen-
dc.format.extent18117~18122-
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBrain/pathology-
dc.subject.MESHCell Line-
dc.subject.MESHCell Movement-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCentral Nervous System/injuries*-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHFibroblast Growth Factor 2/metabolism-
dc.subject.MESHHumans-
dc.subject.MESHHypoxia-
dc.subject.MESHInflammation-
dc.subject.MESHIschemia/pathology-
dc.subject.MESHMice-
dc.subject.MESHMicroscopy, Fluorescence-
dc.subject.MESHModels, Statistical-
dc.subject.MESHNeural Crest/cytology*-
dc.subject.MESHReceptors, CXCR4/metabolism*-
dc.subject.MESHStem Cell Transplantation-
dc.subject.MESHStem Cells/cytology*-
dc.subject.MESHUp-Regulation-
dc.titleDirected migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1 alpha/CXC chemokine receptor 4 pathway-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pediatrics (소아과학)-
dc.contributor.googleauthorYang D. Teng-
dc.contributor.googleauthorDan Frenkel-
dc.contributor.googleauthorMarta Nieto-
dc.contributor.googleauthorFranz-Josef Mueller-
dc.contributor.googleauthorKook In Park-
dc.contributor.googleauthorKhadir Raddassi-
dc.contributor.googleauthorJaime Imitola-
dc.contributor.googleauthorJianxue Li-
dc.contributor.googleauthorRichard L. Sidman-
dc.contributor.googleauthorChristopher A. Walsh-
dc.contributor.googleauthorEvan Y. Snyder-
dc.contributor.googleauthorSamia J. Khoury-
dc.identifier.doi10.1073/pnas.0408258102-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.relation.journalcodeJ02550-
dc.identifier.eissn1091-6490-
dc.identifier.pmid15608062-
dc.subject.keywordhuman stem cells-
dc.subject.keywordhoming-
dc.subject.keywordchain migration-
dc.subject.keywordstroke-
dc.subject.keywordhypoxia–ischemia-
dc.contributor.alternativeNamePark, Kook In-
dc.rights.accessRightsfree-
dc.citation.volume101-
dc.citation.number52-
dc.citation.startPage18117-
dc.citation.endPage18122-
dc.identifier.bibliographicCitationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.101(52) : 18117-18122, 2004-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers

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