Human Neural Stem Cells Genetically Modified to Overexpress Akt1 Provide Neuroprotection and Functional Improvement in Mouse Stroke Model
Identifieur interne : 000B22 ( Pmc/Checkpoint ); précédent : 000B21; suivant : 000B23Human 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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<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>
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<publisher-loc>San Francisco, USA</publisher-loc>
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<article-id pub-id-type="pmc">2679145</article-id>
<article-id pub-id-type="publisher-id">08-PONE-RA-07528R1</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0005586</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline"><subject>Biotechnology/Chemical Biology of the Cell</subject>
<subject>Developmental Biology/Stem Cells</subject>
<subject>Genetics and Genomics/Gene Therapy</subject>
<subject>Neurological Disorders/Cerebrovascular Disease</subject>
</subj-group>
</article-categories>
<title-group><article-title>Human Neural Stem Cells Genetically Modified to Overexpress Akt1 Provide Neuroprotection and Functional Improvement in Mouse Stroke Model</article-title>
<alt-title alt-title-type="running-head">Human Neural Stem Cells</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Lee</surname>
<given-names>Hong J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Kim</surname>
<given-names>Mi K.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Hee J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Seung U.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Medical Research Institute, Chungang University College of Medicine, Seoul, Korea</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Department of Pharmacology, Dankook University School of Medicine, Cheonan, Korea</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Linden</surname>
<given-names>Rafael</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Biofísica da UFRJ, Brazil</aff>
<author-notes><corresp id="cor1">* E-mail: <email>sukim@interchange.ubc.ca</email>
</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: HJL MKK SUK. Performed the experiments: HJL MKK HJK SUK. Analyzed the data: HJL MKK HJK SUK. Wrote the paper: HJL SUK.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2009</year>
</pub-date>
<pub-date pub-type="epub"><day>18</day>
<month>5</month>
<year>2009</year>
</pub-date>
<volume>4</volume>
<issue>5</issue>
<elocation-id>e5586</elocation-id>
<history><date date-type="received"><day>27</day>
<month>11</month>
<year>2008</year>
</date>
<date date-type="accepted"><day>2</day>
<month>4</month>
<year>2009</year>
</date>
</history>
<copyright-statement>Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2009</copyright-year>
<abstract><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>
</abstract>
<counts><page-count count="9"></page-count>
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<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>
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<name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name>
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