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Suicide gene transferred Schwann cells that can be transplanted with short term immunosuppressive therapy

Research Project

Project/Area Number 10671354
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic 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) HIBASAMI Hiroshige  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60024642)
山崎 隆  三重大学, 医学部, 助手 (70230399)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsCultured Schwann cell / Apoptosis / Nerve Growth Factor / Nerve Growth Factor Receptor / Sphingomyelin Cycle / Antisense / Nerve Regeneration / Gene Therapy / シュワン細胞 / 移植 / 末梢神経 / 軸策再生 / 人工神経 / 神経再生 / ビュングナーバンド / ワーラー変性
Research Abstract

Autologous nerve graft is a useful method which has a high axon growth promoting ability, however, the technique has a number of drawbacks including accompanying donor site mobidity and limited donor nerves available, which encourages the use of allogenic nerve graft. Although allogenic nerve graft under immunosuppressive therapy is as effective as autograft, withdrawal of immunosuppressive agents leads to Schwann cell loss and severe nerve degeneration. Theoretically, insidious replacement of rejected cells by autologous Schwann cells can prevent axonal degeneration. So, we try to develop an artificial nerve composed of both allogenic and autogenic Schwann cells and extracellular component. However it became apparent that cultured Schwann cells do not survive for a long period both in vivo and in vitro and are eliminated by apoptosis. We studied the mechanism behind Schwann cell death in peripheral nerve degeneration and regeneration and found that excessive coupling of nerve growth factor(NGF)and its low affinity receptor p75 NTR, although it is essential to propel Schwann cell cohlmn 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. The finding suggests that selective suppression of p75NTR expression by autologous Schwann cells can lead to selective elimination of allogenic Schwann cells. We have developed an antisense therapy for the purpose which can induce partial suppression of p75NTR expression in vitro and maintain the effect for a substantially long period both in vitro and in vivo. We made an artificial nerve containing autologous Schwann cells treated with the antisense and allogenic Schwann cells and have been studying the usefulness of the graft.

Report

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

    (29 results)

All Other

All Publications (29 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: "神経再生の足場"Clinical Neuroscience. 18(11). 35-38 (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] Hitoshi Hirata, et al.,: "Differentiation and apoptosis without DNA fragmentation in cultured Schwann cells derived from Wallerian degenerated nerve."Apoptosis. 3. 353-360 (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, 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hitoshi Hirata: "Schewann 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: "Scaffold for nerve regeneration"Clinical Neuroscience. 18(11). 35-38 (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 cellevenstin peripheral nerve injury and repair through p75NTR."Orthop.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, et al: "Differentiation and apoptosis without DNA fragmentation in cultured Schwann cells derived from Wallerian degenerated nerve."Apoptosis. 3. 353-360 (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, et al: "Schewann cells can induce collateral sprouting from intact axons : An experimental study of end-to-side neororrhaphy using a Y chamber model."Reconstructive Microsurgery. 15. 281-286 (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: "神経再生の足場"Clinical Neuroscience. 18(11). 35-38 (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] Hitoshi Hirata, et al.,: "Differentiation and apoptosis without DNA fragmentation in cultured Schw ann cells derived from Wallerian degenerated nerve."Apoptosis. 3. 353 (1999)

    • Related Report
      2000 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
      2000 Annual Research Report
  • [Publications] 平田仁: "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] Hitoshi Hirata,et al.: "Differentiation and apoptosis 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 intact 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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