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Functional recovery of the demyelinated diseases following transplantation of the genetically-engineering cells.

Research Project

Project/Area Number 09671434
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionSapporo Medical University School of Medicine , Department of Neurosurgery

Principal Investigator

UEDA Teiji  Sapporo Medical University, Sch. Of Med, Dept. Of Neurosurgery, Asso. Prof.., 医学部, 助教授 (90160184)

Co-Investigator(Kenkyū-buntansha) HONMOU Osamu  Sapporo Medical University, Sch. Of Med, Dept. Of Neurosurgery, Senior instructor, 医学部, 助手 (90285007)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsaxon / demyelination / gene / transplantation / stem cell / transporter
Research Abstract

It has generally been assumed that the adult central nervous system (CNS) is incapable of significant self-repair because of a lack of neurogenesis in the adult mammalian CNS. Although we have reported that remyelination of demyelinated CNS axons occurs following transplantation of exogenous glial cells in the animal models, it is still unclear whether transplantation of myelin-forming cell derived from adult humans can remyelinate the demyelinated axons and restore the conduction properties in the adult CNS. To examine this issue, the dorsal columns of the adult rat spinal cord were demyelinated by X-irradiation and intraspinal infections of ethidium bromide. Cell suspensions of myelin-forming cells such as Schwann cells, olfactory ensheathing cells, neural stem cells derived from adult humans were infected into the glial-free lesion site. Light and electron microscopic examination of the dorsal columns revealed cells engaging and myelinating axons in the demyelinated regions 21 days … More after transplantation. In addition, in situ hybridization study with COT-1 DNA probe which is specific to human DNA indicated that the new myelin was formed by the human cells. The dorsal columns were removed and maintained in an in vitro recording chamber; conduction properties were studied using field potential recording techniques. The demyelinated axons exhibited conduction slowing and block, and a reduction in their ability to follow high frequency stimulation. Axons remyelinated by transplantation of myelin-forming cells derived from adult human exhibited restoration of conduction through the lesion, with re-establishment of normal conduction velocity. The axons remyelinated following transplantation showed enhanced impulse recovery to paired pulse stimulation and greater frequency-following capability as compared to both demyelinated axons. These results demonstrate the functional repair of demyelinated axons in the adult CNS by transplantation of myelin-forming cells derived from adult human. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Kato, T. et al.: "Transplantation lf human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord"GLIA. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 本望 修ら: "ヒト胎児脳由来神経幹細胞の神経外傷モデルへの移植"神経外傷. 22(2). 99-103 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato, T. et al.: "Identification of Neural Precursor Cells in the Adult Human Brain : Clonal analysis in vitro"Restorative Neurology and Neuroscience. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honmou, O. et al.: "Transplantation of human neural stem cells repairs the injured central nervous system in the adult rat"Restorative Neurology and Neuroscience. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akiyama, Y. et al.: "Transplantation of clonal neural stem cells derived from adult human brain elicits functional repair of demyelinated spinal cod axons in the adult rat"Restorative Neurology and Neuroscience. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] AKIYAMA,Y., HONMOU, O., KATO,T., UEDE,T., HASHI,K., KOCSIS,J.D.: "Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinalcord."Exp. Neurol.. revised. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KATO,T., HONMOU,O., UEDE,T., HASHI,K., KOCSIS,J.D.: "transplantation of human olfactory ensheathing cells elicits remyelination of demyelination rat spinal cord."GLIA. in press. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NONAKA,T., HONMOU,O., SAKAI,J., HASHI,K., KOCSIS,J.D.: "Excitability changes of dorsal root axons following nerve injury: implications for injury-induced changes in axonal NaィイD1+ィエD1 channels."Brain Res.. 24. 280-258 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KATO,T., HONMOU,O., AKIYAMA,Y., HASHI,K.: "Identification of neural precursor cells in the adult human brain: clonal analysis in vitro"Restorative Neurology and Neuroscience. in press. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., KATO,T., AKIYAMA,Y., HASHI,K.: "transplantation of human neural stem cells repairs the injured central nervous system in the adult rat."Restorative Neurology and Neuroscience. in press. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] AKIYAMA,Y., HONMOU,O., KATO,T., HASHI,K.: "transplantation of clonal neural stem cells derived from adult human brain elicits functional repair of demyelinated spinal cord axons in the adult rat."Restorative Neurology and Neuroscience. in press. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] AKIYAMA,Y., HONMOU,O., KATO,T., KOCSIS,J.D., UEDE,T., HASHI,K.: "Functional repair of demyelinated spinal cord axons in the adult rat by transplantation of clonal neural stem cells derived from adult human brain."Soc. Neurosci. (abst). 1. 213 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KATO,T., HONMOU,O., AKIYAMA,Y., KATO,T., KOCSIS,J.D., UEDE,T., HASHI,K.: "transplantation of human olfactory ensheathing cells to the demyelinated spinal cord."Soc. Neurosci. (abst). 1:211. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] IGARASHI,K., HONMOU,O., AKIYAMA,Y., KATO,T., KOCSIS,J.D., UEDE,T., HASHI,K.: "transplantation of fetal human neural precursor cells repairs demyelinated spinal cord axons in the adult rat"Soc. Neurosci. (abst). 1:213. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., KATO,T., AKIYAMA,Y., KATO,T., KOCSIS,J., UEDE,T., HASHI,K.,: "Clonal analysis of neural stem cells derived from adult human brain"Soc. Neurosci. (abst). 2:2290. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., UEDE,T., SAKAI,J., HASHI,K.: "DNA diagnosis in the NF2 gene."Tumor Res.. 32. 33-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] SAKAI,J., HONMOU,O., KOCSIS,J.D., HASHI,K.: "The delayed depolarization in rat cutaneous afferent axon is reduced following nerve transection and ligation, but not crush: implications for injury-induced axonal Na channel reorganization."Muscle and Nerve.. 21. 1040-1047 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KATO,T., HONMOU,O., KOCSIS,J.D., UEDE,T., HASHI,K.: "Transplantation of human olfactory ensheathing cells to the demyelinated spinal cord."Restorative Neurology and Neuroscience.. 13. 224 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., KATO,T., HASHI,K.: "Transplantation of the genetically-engineering neural stem cell."Restorative Neurology and Neuroscience. 13:230. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., KATO,T., UEDE,T., HASHI,K.: "Studies of myelin formation after transplantation of MHC knockout mouse Schwann cells into the demyelinated rat spinal cord."Soc. Neurosci (abst). 1:69. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., HASHI,K., DUNCAN,I.D., KOCSIS,J.D.: "Comparison of conduction properties of chronically vs chemically-induced demyelinated axons."Restorative Neurology and Neuroscience. 12. 230-231 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., HASHI,K., FELTS,P.A., WAXMAN,S.G., KOCSIS,J.D.: "Functional repair of demyelinated spinal cord axons in the rat by transplantation of genetically-engineering Schwann cells."Clinical Neurology and Neruosurgery, Centennial Perspective, Abstracts of the Free Papers (11ィイD1thィエD1 International Congress of Neurological Surgery). 99 (Supply 1). S143 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., HASHI,K., FELTS,P.A., WAXMAN,S.G., KOCSIS,J.D.: "Functional repair of demyelinated spinal cord axons in the rat by transplantation of genetically-engineering Schwann cells."11ィイD1thィエD1 International Congress of Neurological Surgery. 1909-1912 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] HONMOU,O., HASHI,K., KWIECIEN,J., DUNCAN,I.D., KOCSIS,J.D.: "Comparison of conduction in amyelinated and acute chemically-induced demyelinated axons."Soc. Neurosci (abst). 2. 1726 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] SAKAI,J., HONMOU,O., HASHI,K.: "Reduction of delayed-depolarization in the rat cutaneous afferents following nerve injury."Soc. Neurosci (abst). 2. 1720 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato,T.et al.: "Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord"GLIA. (In press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 本望 修ら: "ヒト胎児脳由来神経幹細胞の神経外傷モデルへの移植"神経外傷. 22(2). 99-103 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kato,T.et al.: "Identification of Neural Precursor Cells in the Adult Human Brain:Clonal analysis in vitro"Restorative Neurology and Neuroscience. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honmou,O.et al.: "Transplantation of human neural stem cells repairs the injured central nervous system in the adult rat"Restorative Neurology and Neuroscience.. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akiyama,Y.et al.: "Transplantation of clonal neural stem cells derived from adult human brain elicits functional repair of demyelinated spinal cod axons in the adult rat"Restorative Neurology and Neuroscience.. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honmou,O., Kato,T., and Hashi,K.: "Transplantation of the genetically engineering neural stem cell." Restorative Neurology and Neuroscience. 23. 230 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kato,T., Honmou,O., Uede,T., and Hashi,K.: "Transplantation of human olfactory ensheathing cells to the demyelinated spinal cord." Restorative Neurology and Neuroscience. 23. 224 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Honmou,O., Kato,T., Uede,T., and Hashi,K.: "Studies of myelin formation after transplantation of MHC knockout mouse Schwann cells into the demyelinated rat spinal cord" Abstract of Society for Neuroscience. 24. 69 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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