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Regeneration of injured central nervous system by cell therapy using neural cell adhesion molecule L1

Research Project

Project/Area Number 08457362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOsaka University

Principal Investigator

ARITA Norio  Osaka University Medical School, Lecturer, 医学部, 講師 (80159508)

Co-Investigator(Kenkyū-buntansha) MORI Kensaku  National Institute of Bioscience and Human Technolgy, Director, フロンティア研究システム・ニューロン機能研究グループ, ディレクター (60008563)
IZUMOTO Shuichi  Osaka University Hospital, Medical staff, 医学部・附属病院, 医員
OHNISHI Takanori  Osaka University Medical School, Assistant Professor, 医学部, 助手 (70233210)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsL1 / cell adhesion molecule / nerve regeneration / optic nerve / nerve injury / visual evoked potential / nerve degeneration / 神経細胞接着分子 / 中枢神経損傷 / 神経再生 / 細胞療法 / 視神経 / neural cell adhesion molecule / neural regeneration
Research Abstract

Optic nerve has been believed not to regenerate in postnatal mammals except if peripheral nerve transplants are offered as a substrate or if treated with transglutaminase. Neural cell adhesion molecule L1 is a member of the immunoglobulin superfamily. L1 plays important roles in neuron-neuron adhesion, neurite fasciculation, neurite outgrowth and neural cell migration. The homophilic binding of L1 in neuronal growth cones to L1 expressed on the surface of the other cells with or without the assistance of NCAM can promote axonal growth. We. Present evidence that -the transected optic nerve in adult rats was promoted to. Regenerate by transplanted L1-expressing cells that were embedded in the Matigel matrix. To obtain the maximum effects, a very careful operative procedure by which both stumps remained attached and the blood supply was preserved, was essential. Visual evoked potential was partially recovered and traced fibers were seen to pass through the lesion 7 weeks after optic nerve transection. Immunohistochemical analysis demonstrated that neurofilament-positive fibers were ; present around the site of experimental lesion. These results present electrophysiological and morphological evidences that the optic nerv& in adult rats has the potential to regenerate if the surrounding matrix contains L1 presenting cells without using peripheral nerve grafts.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Tsuzuki T, Arita N, et al: "Neural cell adhesion molecule L1 in gliomas : correlation with TGF-β and p53." J Clin Pathol. 51. 13-17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumoto S, Arita N, et al: "Neural cell adhesion molecules promotes regeneration of injured optic nerve of rats." Restorative Neurol Neurosci. 12. 247-254 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanemura Y, Arita N, et al: "Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene." FEBS Letters. 442. 151-156 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumoto S, Arita N, et al: "Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion." Cancer Res. 56. 1440-1444 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumoto S, Arita N, et al: "A new mutation of the L1CAM gene in an X-linked hydrocephalus family." Childs Ner Syst. 12. 742-747 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiraga S, Arita N, et al: "Telomerase activity and alterations in telomere length in human brain tumors." Cancer Res. 58. 2117-2125 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumoto S,Ohnishi T,Arita N,Hiraga S,Taki T,Hayakawa H: "Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion." Cancer Res. 56. 1440-1444 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiraga S,Arita N,Ohnishi T,Izumoto S,Taki T,Higuchi M,Iwaisako K,Sakoda S,Yamamoto Y,Hayakawa T: "Establishment of spontaneously immortalized rat type 1 astroglial cell lines : The role of p53 in astroglial carcinogenesis." Glia. 18. 185-199 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumoto S,Yamasaki M,Arita N,Hiraga S,Ohnishi T,Fujitani K,Sakoda S,Hayakawa T: "A new mutation of the L1CAM gene in an X-linked hydrocephalus family." Childs Ner Syst. 12. 742-747 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohnishi T,Arita N,Hiraga S,Taki T,Izumoto S,Fukushima Y,Hayakawa T: "Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity." Clin Exp Metastasis. 15. 538-546 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuzuki T,Izumoto S,Ohnishi T,Hiraga S,Arita N,Hayakawa T: "Neural cell adhesion molecule L1 in gliomas : correlation with TGF-beta and p53." J Clin Pathol. 51. 13-17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukushima Y,Ohnishi T,Arita N,Hayakawa T,Sekiguchi K: "Integrin alpha3beta1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells." Inter Cancer. 76. 63-72 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saitoh Y,Eguchi Y,Hagiwara Y,Arita N,Watahiki M,Tsujimoto Y,Hayakawa T: "Dose-dependent doxycycline-mediated ACTH secretion from encapsulated Tet-on POMC Neuro2A cells in the subarachnoid space." Human Gene Therapy. 9. 997-1002 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiraga S,Ohnishi T,Izumoto S,Miyahara E,Kanemura Y,Matsumura H,Arita N: "Teclomerase activity and alterations in telomere length in human brain tumors." Cancer Res. 58. 2117-2125 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumoto S,Ohnishi T,Hirano S,Hiraga S,Arita N: "Neural cell adhesion molecules promotes regeneration of injured optic nerve of rats." Restorative Neurol Neurosci. 12. 247-254 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanemura Y,Hiraga S,Arita N,Ohnishi T,Izumoto S,Mori K,Matsumura H,Yamasaki M,Fushiki S,Yoshimine T: "Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing (gcm) gene." FEBS Letters. 442. 151-156 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuzuki T,Arita N,et al: "Neural cell adhesion molecule L1 in gliomas:correlation with TGF-β and p53." J Clin Pathol. 51. 13-17 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukushima Y,Arita N,et al: "Integrin α3β.1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells." Inter J Cancer. 76. 63-72 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Saitoh Y,Arita N,et al: "Dose-dependent doxycycline-mediated ACTH secretion from encapsulated Tet-on POMC Neuro2A cells in the subarachnoid space." Human Gene Therapy. 9. 997-1002 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Izumoto S,Arita N,et al: "Neural cell adhesion molecules promotes regeneration of injured optic nerve of rats." Restorative Neurol Neurosci. 12. 247-254 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiraga S,Arita N,et al: "Telomerase activity and alterations in telomere length in human brain tumors." Cancer Res. 58. 2117-2125 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanemura Y,Arita N,et al: "Isolation and expression analysis of a novel human homologue of the Drosophila glial cells missing(gcm)gene." FEBS Letters. 442. 151-156 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Izumoto S: "Gene expression of neural cell adhesion molecule L1 in maligant gliomas and biological ; significance of L1 in glioma invasion." Cancer Research. 56. 1440-1444 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Izumoto S: "A new mutaiton of the L1CAM gene in an X-linked hydrocephalus family." Child's Nervous System. 12. 742-747 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiraga S: "Establishment of spontaneously immortalized rat type 1 astroglial cell lines : the role of p53 in astroglial carcinogenesis." Glia. 18. 185-199 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Izumoto,S: "Microsatellite instability and mutated type II transforming growth factor-β receptor gene in gliomas." Cancer Letters. 122. 251-256 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohnishi T: "Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity." Clinical and Experimental Metastasis. 15. 538-546 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuzuki T: "Neural cell adhesion molecule L1 in gliomas : correlation with TGF-β and p53." Journal of Clinical Pathology. 51. 13-17 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Izumoto S,et al.: "A new mutation of the LICAM gene in an X-linked hydrocephalus family." Child's Nerv Syst. 12. 742-747 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Izumoto S,et al.: "Micorsatellite instability and mutated typell transforming growth factor- receptor gene in gliomas." Cancer letters. 112. 251-256 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiraga S,et al.: "Establishment of spontaneously immortalized rat type I astroglial cell lines : The role of p53 in astroglial carcinogenesis." Glia. 18. 185-199 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Izumoto S,et al.: "Gene expression of nerual cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion." Cancer Res. 56. 1440-1444 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto H,et al.: "Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrin 6 subunit expression." Int J Cancer. 65. 519-524 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Taki T,et al.: "Antisense inhibition of the RAD 51 enhances radiosensitivity" Biochem Biophy Res Comm. 223. 434-438 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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