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Development of hybrid artificial nerve with suicide gene transferred Schwann cells that can be used with short term immunosuppressive therapy

Research Project

Project/Area Number 10557158
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Plastic surgery
Research InstitutionMie University

Principal Investigator

HIRATA Hitoshi  Mie University, Hospital, Lecturer, 医学部・附属病院, 講師 (80173243)

Co-Investigator(Kenkyū-buntansha) NAGAI Hiroshi  KOKEN BIO SCIENCE, Director, 所長 (90013812)
HIBASAMI Hiroshige  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60024642)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥10,400,000 (Direct Cost: ¥10,400,000)
KeywordsArtificial nerve / Schwann cell / Antisense / Nerve Growth Factor / Apoptosis / Nerve Regeneration / 末梢神経再生 / シユワン細胞 / ビュングナーバンド
Research Abstract

The purpose of the present study is to develop a hybrid artificial nerve which is composed of cultured Schwann cells and extacellular matrix component. We successfully established a method to obtain Schwann cells from peripheral nerves of adult animals with high purity and efficiently expand the population in vitro. However it became apparent that cultured Schwann cells do not survive for long both in vivo and in vitro and eliminated by apoptosis. So, we studied the mechanism behind Schwann cell death in peripheral nerve degeneration and regeneration. We have found that excessive coupling of nerve growth factor(NGF)and its low affinity receptor p75 NTR, although it is essential to propel Schwann cell column formation within the basal lamina, could induce Schwann cell apoptosis via sphingomyelin cycle and activation of NF-kB.The intensity of the signal was correlated to the expression levels of p75NTR by Schwann cells. These findings suggest that promotion and maintenance of Schwann cell columns within the scaffold made of extracellular matrix component can be achieved by keeping transcription level of the receptor by Schwann cells at low levels. So, we have explored the possibility of antisense therapy for the purpose. So far, we have succeeded in maintaining Schwann cell columns for a long time while keeping their high axonal growth promoting ability in vitro.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] 平田 仁: "シュワン細胞のアポトーシス"骨・関節・靭帯. 13(8). 885-895 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平田 仁: "培養シュワン細胞を組み込んだハイブリット型人工神経"骨・関節・靭帯. 13(8). 909-917 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata, at al.,: "Nerve growth factor regulates Schwann celleventsin peripheral nerve injury and repair through p75NTR."Orthop. Res, Trans.. 25. 841 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平田 仁: "末梢神経損傷に対するマイクロサージェリーのコツ"Orthopeadics. 12. 39-45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平田 仁、他: "末梢神経の端側吻合"末梢神経. 19(1). 89-96 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平田 仁、他: "マーカイン処理筋を用いた軸索再生誘導"末梢神経. 19(1). 113-117 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata: "Schwann cell apoptosis"HONE KANSETU JINTAI. 13(8). 885-895 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata: "Schwann cell impregnated hybrid artificial nerve"HONE KANSETU JINTAI. 13(8). 909-917 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata, et al.: "Nerve growth factor regulates Schwann cell eventsin peripheral nerve injury and repair through p75NTR."Ortpop.Res, Trans.. 25. 841 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata: "Tips of microsurgical peripheral nerve repair"Orthopeadics. 12. 39-45 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata: "End-to-side neurorraphy"MASYOSINKEI. 19(1). 89-96 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata: "Enhancement of nerve regeneration by bupivacain treated muscles."MASYOSINKEI. 19(1). 113-117 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平田仁: "シュワン細胞のアポトーシス"骨・関節・靭帯. 13(8). 885-895 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 平田仁: "培養シュワン細胞を組み込んだハイブリット型人工神経"骨・関節・靭帯. 13(8). 909-917 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hitoshi Hirata, at al.,: "Nerve growth factor regulates Schwann celleventsin peripheral nerve injury and repair through p75NTR."Orthop.Res, Trans.. 25. 841 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 平田仁: "末梢神経損傷に対するマイクロサージェリーのコツ"Orthopeadics. 12. 39-45 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 平田仁 他: "末梢神経の端側吻合"末梢神経. 19(1). 89-96 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 平田仁 他: "マーカイン処理筋を用いた軸索再生誘導"末梢神経. 19(1). 113-117 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hitoshi Hirata,et al.,: "Differentiation and apoptosls without DNA fragmentation in cultured Schwann cells derived from Wallerian degenerated nerve"Apoptosis. 3. 353 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hitoshi Hirata.et al.,: "Schwann cells can induce collateral sprouting from intact axons : An experimental study of end-to-side neurorrhaphy using a Y chamber model"Reconstructive Microsurgery. 15. 281-286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 平田 仁 他: "培養シュワン細胞を組み込んだハイブリッド型人工神経の研究3次元培養を用いた検討"骨関節軟部組織移植研究会 移植. in press. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 平田 仁 他: "ワーラー変性におけるSchwann細胞のアポトーシス"日本整形外科学会雑誌. 73. S1472 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 平田 仁 他: "末梢神経損傷に対するマイクロサージェリーのコツ"Orthopeadics. 12. 39-45 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hitoshi Hirata.et al.,: "Schwann cell tube formation in a silicone chamber model devoid of axonal regenretion and role of polyamines regnretion"Biogenic Amines. 14. 239-248 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hitoshi Hirata: "Transient damage to the axonal transport system without wallerian degeneration by acute nerve compression" Experimental Neurology. 147(2). 248-255 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Hirata: "Role of ornithine decarboxylase in proliferation of schwann cells during wallerian degeneration and its enhancement by nerve expansion" Muscle & Nerve. 18. 1341-1343 (1995)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Hirata: "Nerve expansion in nerve regeneration:effect of time on induction of omithine decarboxylase and Schwann cell proliferation" Muscle & Nerve. 20(10). 1314-1317 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Hirata: "Schwann cell tube frmation in a silicon chamber model devoid of axonal regeneration and role of polyamines in nerve regeneration" Biogenic Amines. 14(3). 239-248 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 平田 仁: "培養シュワン細胞を組み込んだ人工神経" 人工臓器. 27(5). 774-780 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Hirata: "Differentiation and apoptosis without DNA fragmentation in Cultured Schwann cells derived from wallerian-degenerated nerve" Apoptosis. 3(5)(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hitoshi Hirata: "Schwann cells can induce collateral sprouting from in tact axons.-An experimental study of end-to-side neurorrhaphy using a Y chamber model-" Recons.Microsurg.(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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