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Functional recovery of the cerebral tissue following transplantation of the genetically-engineering bone marrow stem cells.

Research Project

Project/Area Number 14370442
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HONMOU Osamu  Sapporo Medical University School of Medicine, Department of Neurosurgery, Assistant Professor, 医学部, 講師 (90285007)

Co-Investigator(Kenkyū-buntansha) HAMADA Hirofumi  Sapporo Medical University School of Medicine, Department of Molecular Medicine, Professor, 医学部, 教授 (00189614)
HOUKIN Kiyohiro  Sapporo Medical University School of Medicine, Department of Neurosurgery, Professor, 医学部, 教授 (90229146)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
Keywordsadult / gene / human / infarction / neural stem cell / stroke / transplantation / tumor
Research Abstract

Introduction : We have reported that transplantation of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and demyelination. In the present study, we transplanted genetically-engineering bone marrow stem cells into both middle cerebral artery occlusion model rats and brain tumor model rats, to study their potential therapeutic benefit.
Methdos : We have made three genetically-engineering bone marrow stem cells, 1)to immortalize the stem cells with hTERT gene, 2)to promote the neurotrophic effects with BDNF gene, 3)to promote the anti-tumor effect with IL=2 gene. Lesion size was assessed using MR imaging and spectroscopy, and histological methods.
Results : Transplantation of genetically-engineering bone marrow stem cells reduced lesion volume. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain.
Conclusion : This work demonstrates that highly purified genetically-engineering bone marrow stem cells are neuroprotective in cerebral ischemia models. Also, these cells showed the tremendous anti-tumor effects. Thus, a highly purified, expanded, and genetically-engineered cellular component of bone marrow has demonstrated the therapeutic benefits in both cerebral ischemia and brain tumor.

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Iihoshi S, et al.: "A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats"Brain Res.. (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] Kurozumi, K., et al.: "BDNF gene-modified mesencymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model"Mol.Ther.. (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] Nakamura, K., et al.: "Anti-tumor effect of genetically engineered mesenchymal stem cells in a rat glioma model"Can.Ther.. (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] Inoue, M., et al.: "Comparative analysis of remyelinating potential focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord"Glia. 44. 111-118 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kobune, M., et al.: "Telomerized human multipotent mesenchymal cells can differentiate into hemtopoietic and cobblestone area-supporting cells"Exp.Hematol.. 31. 715-722 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Honmou, O.: "Transplantation of adult human neural precursor cells"Pharmacology of Cerebral Ischemia. 23-27 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 佐々木祐典, 本望 修ら: "神経再生医療の基礎知識.特集-脊髄再生・移植に関する基礎知識"脊椎脊髄ジヤーナル. 101-105 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iihoshi S, Honmou O, Houkin K, Hashi K: "Therapeutic window of intravenous administration of autologous bone marrow after cerebral isehemia in adult rats."Brain Res.. 1007. 1-9 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K, Honmou O, Houkin K, Date I, Hamada H.: "BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model."Mol.Ther.. 9. 189-197 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura K, Ito Y, Kawano Y, Kurozumi K, Kobune M, Tsuda H, Bizen A, Honmou O, Hamada H.: "Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model."Gene Ther.. (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] Inoue M, Honmou O, Oka S, Houkin K, Hashi K, Kocsis JD: "Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord."Glia. 44. 111-118 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kobune M, Kawano Y, Ito Y, Chiba H, Nakamura K, Tsuda H, Sasaki K, Dehari H, Uchida H, Honmou O, Takahashi S, Bizen A, Takimoto R, Matsunaga T, Kato J, Kato K, Houkin K, Niitsu Y, Hamada H: "Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells."Exp Hematol. 31. 715-722 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iihoshi S, et al.: "A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats"Brain Res.. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurozumi, K., et al.: "BDNF gene-modified zuesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model"Mol.Ther.. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura, K., et al.: "Anti-tumor effect of genetically engineered mesenchymal stem cells in a rat glioma model"Can.Ther.. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inoue, M., et al.: "Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord"Glia. 44. 111-118 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobune, M., et al.: "Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells"Exp.Hematol.. 31. 715-722 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Honmou, O.: "Transplantation of adult human neural precursor cells"Pharmacology of Cerebral Ischemia. 23-27 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 佐々木祐典, 本望 修: "神経再生医療の基礎知識.特集-脊髄再生・移植に関する基礎知識"脊椎脊髄ジヤーナル. 101-105 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bizen A, et al.: "Transplantation of mesenchymal stem cells derived from the bone marrow into the demyelinated spinal cord"International Congress Series. 1730. 1-5 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Honmou O., et al.: "Transplantation of neural stem cells into ischemic brain"International Congress Series. 1725. 1-6 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本望 修: "骨髄細胞を用いた神経再生医療"Restorative Neurology and Neuroscience. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 飯星智史: "経静脈的自家骨髄細胞移植による脳梗塞の治療"Restorative Neurology and Neuroscience. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 井上道夫: "中枢性脱髄疾患モデルに対する経静脈的自家骨髄移植"Restorative Neurology and Neuroscience. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akiyama Y, et al.: "Remyelination of the spinal cord by intravenous delivery of bone marrow cells"Glia. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本望 修: "神経幹細胞移植のソース. 神経の再生、脳の科学(増刊号)"星和書店. 237 (2003)

    • Related Report
      2002 Annual Research Report

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

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