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Transplantation of neural stem cells into spinal cord injury of adult rats

Research Project

Project/Area Number 14571402
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKEIO UNIVERSITY

Principal Investigator

NAKAMURA Masaya  Keio University, School of Medicine, Associate Professor, 医学部, 講師 (30217898)

Co-Investigator(Kenkyū-buntansha) WATANABE Kota  Keio University, School of Medicine, Assistant, 医学部, 助手 (60317170)
OKANO Hideyuki  Keio University, School of Medicine, Professor, 医学部, 教授 (60160694)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsspinal cord injury / Neural stem cell / Transplantation / Interleukin-6 / regeneration / Collagen type 1 / 齧歯類 / コラーゲン / セマフォリン3A / 細胞外基質 / セマフォリン
Research Abstract

Recently, we have shown that the transplantation of spinal cord-derived neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cord in adult rats, which may correspond to a behavioral recovery. To apply these results to clinical practice, a system for supplying human NSPCs on a large-scale must be established. However, human spinal cord-derived NSPCs are known to have a low proliferation rate, compared with forebrain derived NSPCs. This low proliferate potency limits the feasibility of large-scale spinal cord derived NSPC use. Thus, forebrain-derived NSPCs should be examined as an alternative to spinal cord-derived NSPCs for treatment of spinal cord injuries. In this study, we compared spinal cord-and forebrain-derived NSPCs transplanted into injured spinal cord with respect to their fates in vivo as well as the animals' functional recovery. Both spinal cord-and forebrain derived NSPCs promoted functional recovery in rats with spinal cord injuries. While bo … More th spinal cord-and forebrain-derived NSPCs survived, migrated, and differentiated into neurons, astrocytes and oligodendrocytes in response to the microenvironment within the injured spinal cord after transplantation, forebrain-derived NSPCs differentiated into more neurons and fewer oligodendrocytes, compared to spinal cord-derived NSPCs.
Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin-6 (IL-6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/ STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) in the treatment of acute SCI in mice. MR16-1 not only suppressed the astrocytic differentiation-promoting effect of IL-6 signaling in vitro but also inhibited the development of astrogliosis after SCI in vivo. MR16-1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16-1 compared with control mice. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Nakamura M, et al.: "Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinalcord contusion injury in adult rats."J Neurosci Res.. 69. 925-933 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura M, Houghtling RA, MacArthur L, Bayer BM, et al.: "Differences in cytokine expression profile between acute and secondary injury in adult rat spinal cord."Exp Neurol. 184. 313-325 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okano H, Ogawa Y, Nakamura M, Kaneko S, Iwanami A, et al.: "Transplantation of neural stem cells into the spinal cord after injury."Seminar in Cell & Developmental Biology. 379. 1-8 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada S, Nakamura M, Mikami Y, Shimazaki T, Mihara M, et al.: "Blockade of interleukin -6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury."J Neurosci Res. 76. 265-276 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe K, Nakamura M, Iwanami A, Kanemura Y, et al.: "Comparison between fetal spinal cord-and forebrain-derived neural stem/progenitor cells as a source of transplantation for spinal cord injury."Dev.Neurosci. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Nakaura M, Bregman BS, Koike M, Uchiyama Y, Toyama Y, Okano H.: "Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinalcord contusion injury in adult rats."J Neurosci Res. 69. 925-933 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura M, Houghtling RA, MacArthur L, Bayer BM, Bregman BS.: "Differences in cytokine expression profile between acute and secondary injury in adult rat spinal cord."Exp Neurol. 184(1). 313-325 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okano H, Ogawa Y, Nakamura M, Kaneko S, Iwanami A, Toyama Y.: "Transplantation of neural stem cells into the spinal cord after injury."Seminar in Cell & Developmental Biology. 379. 1-8 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada S, Nakamura M, Mikami Y, Shimazaki T, Mihara M, Ohsugi Y, Yoshizaki K, Kishimoto T, Toyama Y, Okano H.: "Blockade of interleukin -6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury."J Neurosci Res. 69. 265-276 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe K, Nakamura M, Iwanami A, Kanemura Y, Toyama Y, Okano, H.: "Comparison between fetal spinal cord-and forebrain-derived neural stem/progenitor cells as a source of transplantation for spinal cord injury."Dev.Neurosci.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, M., Houghtling, R.A., MacArthur, L., Bayer B.M., Bregman, B.S.: "Differences in cytokine expression profile between acute and secondary injury in adult rat spinal cord."Exp Neurol. 184・1. 313-325 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okada, S., Nakamura, M., et al.: "Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery inexperimental spinal cord injury."J Neurosci Res. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe, K., Nakamura, M., et al.: "Comparison between fetal spinal cord-and forebrain-derived neural stem/progenitor cells as a source of transplantation for spinal cord injury."Dev.Neurosci. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mikami Y, Okano H, Sakaguchi M, Nakamura M, et al.: "Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis, and functional recovery."J Neurosci Res. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Yoshida, Y.Okada, H.Maruiwa, K.Fukuda, M.Nakamura, et al.: "Synaptic Blockade Plays a Major Role in the Neural Disturbance of Experimental Spinal Cord Compression."J Neurotraum. 20. 1365-1376 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中村雅也, 戸山芳昭: "脊髄再生研究の現状と可能性"脊椎脊髄. 16. 284-290 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura M et al.: "Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinalcord contusion injury in adults rats"J Neurosci Res.. 69. 925-933 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura M et al.: "Transplantation of neural stem cells into the spinal cord after injury"Seminar in Cell & Developmental Biology. 379. 1-8 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村雅也, 戸山芳昭: "損傷脊髄への神経幹細胞移植"実験医学. 20. 1301-1306 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村雅也, 戸山芳昭: "整形外科医のための分子生物学 神経幹細胞と神経栄養因子について"関節外科. 21. 372-375 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村雅也, 岡野栄之: "脊髄損傷に対する再生医療/神経幹細胞移植を中心として"脊椎脊髄. 16. 123-129 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中村雅也, 戸山芳昭: "中枢神経系の再生医学"日本医師会雑誌. 129. 355-359 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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