MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke

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dc.contributor.author Tseng, Kuan-Yin
dc.contributor.author Anttila, Jenni E.
dc.contributor.author Khodosevich, Konstantin
dc.contributor.author Tuominen, Raimo K.
dc.contributor.author Lindahl, Maria
dc.contributor.author Domanskyi, Andrii
dc.contributor.author Airavaara, Mikko
dc.date.accessioned 2018-03-16T09:01:02Z
dc.date.available 2018-03-16T09:01:02Z
dc.date.issued 2018-01-03
dc.identifier.citation Tseng , K-Y , Anttila , J E , Khodosevich , K , Tuominen , R K , Lindahl , M , Domanskyi , A & Airavaara , M 2018 , ' MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke ' , Molecular therapy , vol. 26 , no. 1 , pp. 238-255 . https://doi.org/10.1016/j.ymthe.2017.09.019
dc.identifier.other PURE: 100445596
dc.identifier.other PURE UUID: 4b18e361-77c3-481d-9a8c-a7ae5c888cc7
dc.identifier.other WOS: 000423013500024
dc.identifier.other Scopus: 85031508541
dc.identifier.other Bibtex: urn:417d109ed58661ce3725956bf19fdd1d
dc.identifier.other ORCID: /0000-0002-2026-1609/work/42819732
dc.identifier.other ORCID: /0000-0002-5674-8830/work/68614608
dc.identifier.uri http://hdl.handle.net/10138/233497
dc.description.abstract Cerebral ischemia activates endogenous reparative processes, such as increased proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and migration of neural progenitor cells (NPCs) toward the ischemic area. However, this reparative process is limited because most of the NPCs die shortly after injury or are unable to arrive at the infarct boundary. In this study, we demonstrate for the first time that endogenous mesencephalic astrocyte-derived neurotrophic factor (MANF) protects NSCs against oxygen-glucose-deprivation-induced injury and has a crucial role in regulating NPC migration. In NSC cultures, MANF protein administration did not affect growth of cells but triggered neuronal and glial differentiation, followed by activation of STAT3. In SVZ explants, MANF over expression facilitated cell migration and activated the STAT3 and ERK1/2 pathway. Using a rat model of cortical stroke, intracerebroventricular injections of MANF did not affect cell proliferation in the SVZ, but promoted migration of doublecortin (DCX)(+) cells toward the corpus callosum and infarct boundary on day 14 post-stroke. Long-term infusion of MANF into the per'-infarct zone increased the recruitment of DCX+ cells in the infarct area. In conclusion, our data demonstrate a neuroregenerative activity of MANF that facilitates differentiation and migration of NPCs, thereby increasing recruitment of neuroblasts in stroke cortex. en
dc.format.extent 18
dc.language.iso eng
dc.relation.ispartof Molecular therapy
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject NEUROTROPHIC FACTOR MANF
dc.subject ISCHEMIC BRAIN-INJURY
dc.subject SPINAL-CORD-INJURY
dc.subject GROWTH-FACTOR
dc.subject SUBVENTRICULAR ZONE
dc.subject ADULT NEUROGENESIS
dc.subject STRIATAL NEUROGENESIS
dc.subject NEUROBLAST MIGRATION
dc.subject DOPAMINERGIC-NEURONS
dc.subject PARKINSONS-DISEASE
dc.subject 1184 Genetics, developmental biology, physiology
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke en
dc.type Article
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization Faculty of Pharmacy
dc.contributor.organization Division of Pharmacology and Pharmacotherapy
dc.contributor.organization Regenerative pharmacology group
dc.contributor.organization Drug Research Program
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.ymthe.2017.09.019
dc.relation.issn 1525-0016
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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