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A genetically-engineering bone marrow stem cell therapy for stroke

Research Project

Project/Area Number 16390414
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, Assistant Professor (90285007)

Co-Investigator(Kenkyū-buntansha) HOUKIN Kiyohiro  Sapporo Medical University, School of Medicine, Professor (90229146)
HAMADA Hirofumi  Sapporo Medical University, School of Medicine, Professor (00189614)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥15,250,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywordsadult / gene / human / infarction / neural stem cell / stroke / transplantation / gene / human / infarction / neuroprotection / stroke / transplantation
Research Abstract

Introduction : We have reported that transplantation of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia. In the present study, we transplanted genetically-engineering bone marrow stem cells into middle cerebral artery occlusion model rats to study their potential therapeutic benefit.
Methdos : We have made five 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 neurotrophic effects with GDNF gene, 4) to promote the angiogenetic effects with Ang-1 gene, 5) to promote the angiogenetic effects with P1GF 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 was correlated with subsequent histological examination of the brain.
Conclusion : This work demonstrates that highly purified genetically-engineering bone marrow stem cells are neuroprotective and angeigenetic in cerebral ischemia models. Thus, a highly purified, expanded, and genetically-engineered cellular component of bone marrow has demonstrated the therapeutic benefits in cerebral ischemia.

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2008 2007 2006 2005 2004

All Journal Article (26 results) (of which Peer Reviewed: 4 results) Presentation (8 results) Book (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Therapeutic benefits by Ang-1 gene-modified human mesenchymal stem cells after cerebral ischemia.2008

    • Author(s)
      Onda, et. al.
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism 28

      Pages: 329-340

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Therapeutic benefits by Ang-1 gene-modified2008

    • Author(s)
      Onda, T., Honmou, O., Harada, K, Houkin, K., Hamada, H., Koosis, J.D
    • Journal Title

      human mesenchvmal stem cells after cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism 28

      Pages: 329-340

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mesenchymal stem cells derived from peripheral blood protects against ischexnia2007

    • Author(s)
      Ukai, et. al.
    • Journal Title

      J Neurotrauma 24

      Pages: 508-520

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Magnetic resonance lactate and lipid signals in rat brain after middle cerebral artery occlusion model2007

    • Author(s)
      Harada, et. al.
    • Journal Title

      Brain Research 1134

      Pages: 206-213

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells derived from peripheral blood protects against ischemia2007

    • Author(s)
      Ukai, R., Honmou, O., Harada, K., Houkin, K, Hamada, H., Kocsis, J.D
    • Journal Title

      J Neurotrauma 24(3)

      Pages: 508-520

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Magnetic resonance lactate and lipid signals in rat brain after middle cerebral artery occlusion model2007

    • Author(s)
      Harada, K., Honmou, O., Liu H., Bando, M., Houkin, K., Kocsis, J.D
    • Journal Title

      Brain Research 1134

      Pages: 206-213

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mesenchymal stem cells derived from peripheral blood protects against ischemia2007

    • Author(s)
      Ukai, et. al.
    • Journal Title

      J Neurotrauma 24

      Pages: 508-520

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells derived from peripheral blood protects against ischemia2007

    • Author(s)
      Ukai et al.
    • Journal Title

      J Neurotrauma 24

      Pages: 508-520

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Magnetic resonance lactate and lipid signals in rat brain after middle cerebral artery occlusion model2007

    • Author(s)
      Harada et al.
    • Journal Title

      Brain Research 1134

      Pages: 206-213

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Neural differentiation potential of peripheral blood- and bone marrow-derived precursor cells2006

    • Author(s)
      Kim, S., Honmou, O., Kato, K., Nonaka, T., Houkin, K., Hamada, H., Kocsis, J.D
    • Journal Title

      Brain Research 1123, 19

      Pages: 27-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Intravenous administration of GDNF gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2006

    • Author(s)
      Horita, Y., Honmou, O., Harada, K., Houkin, K., Hamada, H., Kocsis, J.D
    • Journal Title

      J.Neuroscience Research 84

      Pages: 1495-1504

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischemia2006

    • Author(s)
      Liu, H., Honmou, O., Harada, K., Nakamura, K., Houkin, K., Hamada, H., Kocsis, J.D
    • Journal Title

      BRAIN 129

      Pages: 2734-2745

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2006

    • Author(s)
      Honma, T., Honmou, O., Iihoshi, S., Houkin, K., Hamada, H., Kocsis, J.D
    • Journal Title

      Exp Neurol 199

      Pages: 56-66

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Neural differentiation potential of peripheral blood- and bone marrow-derived precursor cells2006

    • Author(s)
      Kim et al.
    • Journal Title

      Brain Research 1123

      Pages: 27-33

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intravenous administration of GDNF gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2006

    • Author(s)
      Horita et al.
    • Journal Title

      J. Neuroscience Research 84

      Pages: 1495-1504

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Neuroprotection by PIGF gene-modified human mesenchymal stem cells after cerebral ischemia2006

    • Author(s)
      Liu et al.
    • Journal Title

      BRAIN 129

      Pages: 2734-2745

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2006

    • Author(s)
      Honma et al.
    • Journal Title

      Exp Neurol 199

      Pages: 56-66

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intravenous infusion of BDNF gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2005

    • Author(s)
      Nomura, T., Honmou, O., Harada, H., Houkin, K., Hamada, H., Kocsis, J.D
    • Journal Title

      Neuroscience 136

      Pages: 161-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model2005

    • Author(s)
      Kurosumi, K., Nakaniura, 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
    • Journal Title

      Mol. Ther 11(1)

      Pages: 96-104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2005

    • Author(s)
      Nomura, T., et al.
    • Journal Title

      Neuroscience 136

      Pages: 161-169

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat2005

    • Author(s)
      Honma, T., et al.
    • Journal Title

      Experimental Neurology (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model2005

    • Author(s)
      Kurosumi, K., et al.
    • Journal Title

      Mol.Ther. 11

      Pages: 96-104

    • Related Report
      2005 Annual Research Report 2004 Annual Research Report
  • [Journal Article] Mesenchymal stem cells as therapeutic cytoreagents for gene therapy2005

    • Author(s)
      Hamada, H., et al.
    • Journal Title

      Cancer Sci 96

      Pages: 149-156

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mesenchymal stem cells as therapeutic cytoreagents for gene therapy2005

    • Author(s)
      Hamada, H., et al.
    • Journal Title

      Cancer Sci (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model2004

    • Author(s)
      Kurosumi, K., et al.
    • Journal Title

      Mol Ther. 9

      Pages: 189-197

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats2004

    • Author(s)
      Iihoshi, S., et al.
    • Journal Title

      Brain Res. 1007

      Pages: 1-9

    • Related Report
      2004 Annual Research Report
  • [Presentation] 脳梗塞に対する骨髄幹細胞治療2007

    • Author(s)
      本望 修
    • Organizer
      日本脳神経外科学会総会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Recent advance of regenrative medicine2007

    • Author(s)
      Honmou, O
    • Organizer
      The 12th Asian-Australasian Congress of Neurological Surgeons
    • Place of Presentation
      Nagoya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intravenous administration of mesenchymal stem cells derived from peripheral blood repairs the ischemic lesions in the rat middle cerebral artery occlusion model2006

    • Author(s)
      Honmou, O.,Ukai, R., Harada, K.,Houkin, K
    • Organizer
      36th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Atlanta
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intravenous administration of cytokine gene-modifued human mesenchymal stem cells repairs the ischemic lesions in the rat middle cerebral artery occlusion model2006

    • Author(s)
      Honmou, O
    • Organizer
      2nd Annual Stem Cell Research & Therapeutics
    • Place of Presentation
      San Francisco
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Comparison between peripheral blood-derived and bone marrowAderived stem cells for neural differentiation2005

    • Author(s)
      Honmou, O., Houkin, K., Kocsis, JD
    • Organizer
      35th Annual Meeting Society for Neuroscience
    • Place of Presentation
      Washington
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A cell therapy for the CNS diseases2005

    • Author(s)
      Honraou, O
    • Organizer
      6th International Congress on Minimally Invasive Neurosurgery & 3rd World Congress of the Academy for Multidisciplinary Neurotraumatology
    • Place of Presentation
      Nagoya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Anti-tumor effect of IL2 gene-modified mesenchymal stem cells in a rat glioma model2005

    • Author(s)
      Honmou, O
    • Organizer
      6th International Congress on Minimally Invasive Neurosurgery & 3 r d World Congress of the Academy for Multidisciplinary Neurotraumatology
    • Place of Presentation
      Nagoya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intravenous administration of immortalized human mesenchymal stem cells repairs the ischemic leisions in the rat middle cerebral artery occulusion model2004

    • Author(s)
      Honmou, O., Iihoshi, S., Honma, T., Harada, K., Hamada, H., Houkin K., Kocsis, JD
    • Organizer
      34th Annual Meeting of Society for Neuroscience
    • Place of Presentation
      San Diego
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 骨髄幹細胞を用いた再生医療2007

    • Author(s)
      本望 修
    • Total Pages
      3
    • Publisher
      ライフメディコム
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 脳梗塞の細胞療法2006

    • Author(s)
      本望 修
    • Total Pages
      3
    • Publisher
      日本臨床
    • Related Report
      2006 Annual Research Report
  • [Book] 特集「各科話題の先端医療-再生医療・移植医療-(II)」幹細胞移植による神経再生の臨床応用へ向けて2004

    • Author(s)
      本望 修
    • Publisher
      札医通信
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞増殖方法ならびに組織の修復および再生のための医薬2007

    • Inventor(s)
      本望修 ら
    • Industrial Property Rights Holder
      札幌医科大学 ら
    • Filing Date
      2007-09-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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