Transplantation of human neural stem cells transduced with Olig2 transcription factor improves locomotor recovery and enhances myelination in the white matter of rat spinal cord following contusive injury
Identifieur interne : 001D55 ( Main/Exploration ); précédent : 001D54; suivant : 001D56Transplantation of human neural stem cells transduced with Olig2 transcription factor improves locomotor recovery and enhances myelination in the white matter of rat spinal cord following contusive injury
Auteurs : Dong H. Hwang [Corée du Sud] ; Byung G. Kim [Corée du Sud] ; Eun J. Kim [Corée du Sud] ; Seung I. Lee [Corée du Sud] ; In S. Joo [Corée du Sud] ; Haeyoung Suh-Kim [Corée du Sud] ; Seonghyang Sohn [Corée du Sud] ; Seung U. Kim [Corée du Sud, Canada]Source :
- BMC Neuroscience [ 1471-2202 ] ; 2009.
Abstract
Contusive spinal cord injury is complicated by a delayed loss of oligodendrocytes, resulting in chronic progressive demyelination. Therefore, transplantation strategies to provide oligodendrocyte lineage cells and to enhance the extent of myelination appear to be justified for spinal cord repair. The present study investigated whether transplantation of human neural stem cells (NSCs) genetically modified to express Olig2 transcription factor, an essential regulator of oligodendrocyte development, can improve locomotor recovery and enhance myelination in a rat contusive spinal cord injury model.
HB1.F3 (F3) immortalized human NSC line was transduced with a retroviral vector encoding
Transplantation of NSCs genetically modified to differentiate into an oligodendrocytic lineage may be an effective strategy to improve functional outcomes following spinal cord trauma. The present study suggests that molecular factors governing cell fate decisions can be manipulated to enhance reparative potential of the cell-based therapy.
Url:
DOI: 10.1186/1471-2202-10-117
PubMed: 19772605
PubMed Central: 2758886
Affiliations:
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Kim</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Department of Neurology, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Neurology, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Eun J" sort="Kim, Eun J" uniqKey="Kim E" first="Eun J" last="Kim">Eun J. Kim</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Seung I" sort="Lee, Seung I" uniqKey="Lee S" first="Seung I" last="Lee">Seung I. 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Kim</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="I5">Medical Research Institute, Chungang University School of Medicine, Seoul, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chungang University School of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</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></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19772605</idno><idno type="pmc">2758886</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758886</idno><idno type="RBID">PMC:2758886</idno><idno type="doi">10.1186/1471-2202-10-117</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000331</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000331</idno><idno type="wicri:Area/Pmc/Curation">000331</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000331</idno><idno type="wicri:Area/Pmc/Checkpoint">000A80</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A80</idno><idno type="wicri:Area/Ncbi/Merge">000B51</idno><idno type="wicri:Area/Ncbi/Curation">000B51</idno><idno type="wicri:Area/Ncbi/Checkpoint">000B51</idno><idno type="wicri:Area/Main/Merge">001F01</idno><idno type="wicri:Area/Main/Curation">001D55</idno><idno type="wicri:Area/Main/Exploration">001D55</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transplantation of human neural stem cells transduced with Olig2 transcription factor improves locomotor recovery and enhances myelination in the white matter of rat spinal cord following contusive injury</title><author><name sortKey="Hwang, Dong H" sort="Hwang, Dong H" uniqKey="Hwang D" first="Dong H" last="Hwang">Dong H. Hwang</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Byung G" sort="Kim, Byung G" uniqKey="Kim B" first="Byung G" last="Kim">Byung G. Kim</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Department of Neurology, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Neurology, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Eun J" sort="Kim, Eun J" uniqKey="Kim E" first="Eun J" last="Kim">Eun J. Kim</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Seung I" sort="Lee, Seung I" uniqKey="Lee S" first="Seung I" last="Lee">Seung I. Lee</name><affiliation wicri:level="1"><nlm:aff id="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Joo, In S" sort="Joo, In S" uniqKey="Joo I" first="In S" last="Joo">In S. Joo</name><affiliation wicri:level="1"><nlm:aff id="I2">Department of Neurology, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Neurology, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Suh Kim, Haeyoung" sort="Suh Kim, Haeyoung" uniqKey="Suh Kim H" first="Haeyoung" last="Suh-Kim">Haeyoung Suh-Kim</name><affiliation wicri:level="1"><nlm:aff id="I3">Department of Anatomy, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Anatomy, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Sohn, Seonghyang" sort="Sohn, Seonghyang" uniqKey="Sohn S" first="Seonghyang" last="Sohn">Seonghyang Sohn</name><affiliation wicri:level="1"><nlm:aff id="I4">Laboratory of Cell Biology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Cell Biology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</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="I1">Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Brain Disease Research Center, Institute for Medical Sciences, Ajou University School of Medicine, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="I5">Medical Research Institute, Chungang University School of Medicine, Seoul, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chungang University School of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada</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></analytic><series><title level="j">BMC Neuroscience</title><idno type="eISSN">1471-2202</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Contusive spinal cord injury is complicated by a delayed loss of oligodendrocytes, resulting in chronic progressive demyelination. Therefore, transplantation strategies to provide oligodendrocyte lineage cells and to enhance the extent of myelination appear to be justified for spinal cord repair. The present study investigated whether transplantation of human neural stem cells (NSCs) genetically modified to express Olig2 transcription factor, an essential regulator of oligodendrocyte development, can improve locomotor recovery and enhance myelination in a rat contusive spinal cord injury model.</p></sec><sec><title>Results</title><p>HB1.F3 (F3) immortalized human NSC line was transduced with a retroviral vector encoding <italic>Olig2</italic>, an essential regulator of oligodendrocyte development. Overexpression of Olig2 in human NSCs (F3.Olig2) induced activation of NKX2.2 and directed differentiation of NSCs into oligodendrocyte lineage cells <italic>in vitro</italic>. Introduction of Olig2 conferred higher proliferative activity, and a much larger number of F3.Olig2 NSCs were detected by 7 weeks after transplantation into contused spinal cord than that of parental F3 NSCs. F3.Olig2 NSCs exhibited frequent migration towards the white matter, whereas F3 NSCs were mostly confined to the gray matter or around the lesion cavities. Most of F3.Olig2 NSCs occupying the spared white matter differentiated into mature oligodendrocytes. Transplantation of F3.Olig2 NSCs increased the volume of spared white matter and reduced the cavity volume. Moreover, F3.Olig2 grafts significantly increased the thickness of myelin sheath around the axons in the spared white matter. Finally, animals with F3.Olig2 grafts showed an improvement in the quality of hindlimbs locomotion.</p></sec><sec><title>Conclusion</title><p>Transplantation of NSCs genetically modified to differentiate into an oligodendrocytic lineage may be an effective strategy to improve functional outcomes following spinal cord trauma. The present study suggests that molecular factors governing cell fate decisions can be manipulated to enhance reparative potential of the cell-based therapy.</p></sec></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><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="Corée du Sud"><noRegion><name sortKey="Hwang, Dong H" sort="Hwang, Dong H" uniqKey="Hwang D" first="Dong H" last="Hwang">Dong H. Hwang</name></noRegion><name sortKey="Joo, In S" sort="Joo, In S" uniqKey="Joo I" first="In S" last="Joo">In S. Joo</name><name sortKey="Kim, Byung G" sort="Kim, Byung G" uniqKey="Kim B" first="Byung G" last="Kim">Byung G. Kim</name><name sortKey="Kim, Byung G" sort="Kim, Byung G" uniqKey="Kim B" first="Byung G" last="Kim">Byung G. Kim</name><name sortKey="Kim, Eun J" sort="Kim, Eun J" uniqKey="Kim E" first="Eun J" last="Kim">Eun J. Kim</name><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U" last="Kim">Seung U. Kim</name><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U" last="Kim">Seung U. Kim</name><name sortKey="Lee, Seung I" sort="Lee, Seung I" uniqKey="Lee S" first="Seung I" last="Lee">Seung I. Lee</name><name sortKey="Sohn, Seonghyang" sort="Sohn, Seonghyang" uniqKey="Sohn S" first="Seonghyang" last="Sohn">Seonghyang Sohn</name><name sortKey="Suh Kim, Haeyoung" sort="Suh Kim, Haeyoung" uniqKey="Suh Kim H" first="Haeyoung" last="Suh-Kim">Haeyoung Suh-Kim</name></country><country name="Canada"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U" last="Kim">Seung U. Kim</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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