Human Neural Stem Cells Genetically Modified to Overexpress Akt1 Provide Neuroprotection and Functional Improvement in Mouse Stroke Model
Identifieur interne : 001E42 ( Main/Exploration ); précédent : 001E41; suivant : 001E43Human Neural Stem Cells Genetically Modified to Overexpress Akt1 Provide Neuroprotection and Functional Improvement in Mouse Stroke Model
Auteurs : Hong J. Lee [Canada, Corée du Sud] ; Mi K. Kim [Canada] ; Hee J. Kim [Canada, Corée du Sud] ; Seung U. Kim [Canada, Corée du Sud]Source :
- PLoS ONE [ 1932-6203 ] ; 2009.
Abstract
In a previous study, we have shown that human neural stem cells (hNSCs) transplanted in brain of mouse intracerebral hemorrhage (ICH) stroke model selectively migrate to the ICH lesion and induce behavioral recovery. However, low survival rate of grafted hNSCs in the brain precludes long-term therapeutic effect. We hypothesized that hNSCs overexpressing Akt1 transplanted into the lesion site could provide long-term improved survival of hNSCs, and behavioral recovery in mouse ICH model. F3 hNSC was genetically modified with a mouse Akt1 gene using a retroviral vector. F3 hNSCs expressing Akt1 were found to be highly resistant to H2O2-induced cytotoxicity
Url:
DOI: 10.1371/journal.pone.0005586
PubMed: 19440551
PubMed Central: 2679145
Affiliations:
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Lee</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Medical Research Institute, Chungang University College of Medicine, Seoul, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chungang University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Kim, Mi K" sort="Kim, Mi K" uniqKey="Kim M" first="Mi K." last="Kim">Mi K. 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Lee</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Medical Research Institute, Chungang University College of Medicine, Seoul, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chungang University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Kim, Mi K" sort="Kim, Mi K" uniqKey="Kim M" first="Mi K." last="Kim">Mi K. Kim</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Hee J" sort="Kim, Hee J" uniqKey="Kim H" first="Hee J." last="Kim">Hee J. Kim</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Department of Pharmacology, Dankook University School of Medicine, Cheonan, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Pharmacology, Dankook University School of Medicine, Cheonan</wicri:regionArea><wicri:noRegion>Cheonan</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Medical Research Institute, Chungang University College of Medicine, Seoul, Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chungang University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In a previous study, we have shown that human neural stem cells (hNSCs) transplanted in brain of mouse intracerebral hemorrhage (ICH) stroke model selectively migrate to the ICH lesion and induce behavioral recovery. However, low survival rate of grafted hNSCs in the brain precludes long-term therapeutic effect. We hypothesized that hNSCs overexpressing Akt1 transplanted into the lesion site could provide long-term improved survival of hNSCs, and behavioral recovery in mouse ICH model. F3 hNSC was genetically modified with a mouse Akt1 gene using a retroviral vector. F3 hNSCs expressing Akt1 were found to be highly resistant to H<sub>2</sub>O<sub>2</sub>-induced cytotoxicity <italic>in vitro</italic>. Following transplantation in ICH mouse brain, F3.Akt1 hNSCs induced behavioral improvement and significantly increased cell survival (50–100% increase) at 2 and 8 weeks post-transplantation as compared to parental F3 hNSCs. Brain transplantation of hNSCs overexpressing Akt1 in ICH animals provided functional recovery, and survival and differentiation of grafted hNSCs. These results indicate that the F3.Akt1 human NSCs should be a great value as a cellular source for the cellular therapy in animal models of human neurological disorders including ICH.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Corée du Sud</li></country><settlement><li>Séoul</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Lee, Hong J" sort="Lee, Hong J" uniqKey="Lee H" first="Hong J." last="Lee">Hong J. Lee</name></noRegion><name sortKey="Kim, Hee J" sort="Kim, Hee J" uniqKey="Kim H" first="Hee J." last="Kim">Hee J. Kim</name><name sortKey="Kim, Mi K" sort="Kim, Mi K" uniqKey="Kim M" first="Mi K." last="Kim">Mi K. Kim</name><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></country><country name="Corée du Sud"><noRegion><name sortKey="Lee, Hong J" sort="Lee, Hong J" uniqKey="Lee H" first="Hong J." last="Lee">Hong J. Lee</name></noRegion><name sortKey="Kim, Hee J" sort="Kim, Hee J" uniqKey="Kim H" first="Hee J." last="Kim">Hee J. Kim</name><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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