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COMPREHENSIVE RESEARCH PROJECT FOR CENTRAL NERVOUS SYSTEM REGENERATION BY BONE MARROW STROMAL CELL TRANSPLANTATION

Research Project

Project/Area Number 17390389
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HIDA Kazutoshi  Hokkaido University, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR (10238305)

Co-Investigator(Kenkyū-buntansha) KURODA Satoshi  Hokkaido University, HOSPITAL, LECTURER (10301904)
IWASAKI Yoshinobu  Hokkaido Unive., GRADUATE SCHOOL OF MEDICINE, PROFESSOR (00113522)
YANO Shunsuke  Hokkaido University, HOSPITAL, ASSOCLATE PROFESSOR (20374481)
小林 浩之  北海道大学, 病院, 助教 (70374478)
中山 若樹  北海道大学, 北海道大学病院, 助手 (40421961)
七戸 秀夫  北海道大学, 病院・医員 (80374479)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,670,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2006: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsCerebral infarction / Spinal cord injury / Bone marrow stromal cell / Transplantation / Diffuse axonal injury / Differentiation / Regenerative medicine / Functional restoration / Diffuse brain injury / Cognitive function / DNA microarray / Cerebral stroke / Migration / Biomaterial / Neuroprotection
Research Abstract

We isolated the BMSC from the green fluorescence protein (GFP)-transgenic mice and transplanted them into the mice subjected to spinal cord injury. We could visualize the transplanted cells through the dura mater in the living animals for 4 weeks after transplantation, using a novel fluorescence imaging technique. These data were published in J Neurotrauma (2005). Furthermore, we have confirmed that the transplanted BMSC could improve the GABA receptor function around cerebral infarction and spinal cord injury, using autoradiography and fluorescence immunostaining. These data were published in J Nucl Med (2006) and J Neurotrauma (2007). We also found that the BMSC actively repeat cell proliferation when transplanted into infarct brain, and published the data in Brain Res (2005). We assessed gene expression profile in the cultured BMSC and clarified that the BMSC have the potential to alter their gene expression profile in response to external stimuli. The data were published in Brain Res (2006). We have clarified that the BMSC have the potential to degrade the extracellular matrix in the spinal cord and produce the chemo-attractant factor for axon elongation of the neurons, using a novel "in vitro transplantation" model. The data have been submitted to Neurorehab and Neural Repair. We have also clarified that CXCR4/SDF-1 system is essential in the proliferation and migration of the transplanted BMSC, using the CXCR4-knock out mice. The data have been submitted to Brain Res. Using co-culture paradigm, we have also clarified that the BMSC have the potential to differentiate into the neural cells and protect the neurons exposed to glutamate. The data have been submitted to J Neurosci Res. We have also found that fibrin glue is a suitable biomaterial as a scaffold for the BMSC when transplanted into brain cold injury model or spinal cord hemi-section model of the rats. These data has been prepared for submission to Neurosurgery and J Neurotrauma.

Report

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

    (54 results)

All 2008 2007 2006 2005 Other

All Journal Article (46 results) (of which Peer Reviewed: 15 results) Presentation (4 results) Book (4 results)

  • [Journal Article] Bone marrow stromal cells protect and repair damaged neurons through multiple mechanisms.2008

    • Author(s)
      Hokari M, et. al.
    • Journal Title

      J Neurosci Res 86

      Pages: 1024-1035

    • 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] Bone marrow stromal cells differentiate into neurons and promote axon elongation in spinal cord slice cultures:their role in cell transplantation therapy for spinal cord injury.2008

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

      Neurorehab and Neural Repair (In press)

    • 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] 骨髄間質細胞を用いた損傷脊髄の再生2008

    • Author(s)
      千葉泰弘, ら
    • Journal Title

      リハビリテーション医学 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow stromal cells protect and repair damaged neurons through multiple mechanisms.2008

    • Author(s)
      Hokari M , et. al.
    • Journal Title

      J Neurosci Res 86

      Pages: 1024-1035

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow stromal cells protect and repair damaged neurons…2008

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

      J Neurosci Res 86

      Pages: 1024-1035

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct.2007

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

      Brain Res 1183

      Pages: 138-147

    • 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] 骨髄間質細胞を用いた脊髄損傷の再生2007

    • Author(s)
      黒田 敏, ら
    • Journal Title

      脊椎脊髄ジャーナル 20

      Pages: 1233-1237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 脳損傷の病態と高次脳機能障害-再生治療の展望-2007

    • Author(s)
      丸一勝彦, ら
    • Journal Title

      脳外 35

      Pages: 965-969

    • 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] Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct.2007

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

      Brain Res 1183

      Pages: 138-147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow stromal cell transplantation for spinal cord injury.2007

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

      Spine & Spinal Cord 20

      Pages: 1233-1237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Pathophysiology of cognitive dysfunction after traumatic brain injury-perspective of regenerative medicine2007

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

      Noshinkei Geka 35

      Pages: 965-969

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of SDF-1/CXCR4 system in survival and migration of…2007

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

      Brain Res 1183

      Pages: 138-147

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脳SPECT/PETによる選択的神経細胞障害のイメージング2007

    • Author(s)
      黒田 敏
    • Journal Title

      分子脳血管病 6

      Pages: 293-299

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 骨髄間質細胞を用いた脊髄損傷の再生2007

    • Author(s)
      黒田 敏
    • Journal Title

      脊椎脊髄ジャーナル 20

      Pages: 1233-1237

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 脳損傷の病態と高次脳機能障害-再生治療の展望-2007

    • Author(s)
      丸一勝彦
    • Journal Title

      脳外 35

      Pages: 965-969

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells:An autoradiographic and hist ologic analysis2006

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

      J Nucl Med 47

      Pages: 486-491

    • 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] Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation is associated with intracellular reactive oxygen species.2006

    • Author(s)
      Niiya Y, et. al.
    • Journal Title

      Brain Res 1108

      Pages: 179-187

    • 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] The effects of neuronal induction on gene expression profile in bone marrow stromal cells(BMSC)-A preliminary study using microarray analysis2006

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

      Brain Res 1087

      Pages: 15-27

    • 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] Bone marrow stromal cell transplantation preserves gamma-aminobutyric acid(GABA)receptor function in injured spinal cord.2006

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

      J Neurotrauma 23

      Pages: 1682-1692

    • 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] 骨髄間質細胞を用いた脊髄損傷の再生は"Mission Impossible"か?2006

    • Author(s)
      黒田 敏, ら
    • Journal Title

      分子脳血管病 5

      Pages: 436-442

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: An autoradiographic and histologic analysis2006

    • Author(s)
      Shichinohe H, Kuroda S , et. al.
    • Journal Title

      J Nucl Med 47

      Pages: 1-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC) -A preliminary study using microarray analysis2006

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

      Brain Res 1087

      Pages: 15-27

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow stromal cell transplantation preserves gamma-aminobutyric acid (GABA) receptor function in injured spinal cord.2006

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

      J Neurotrauma 23

      Pages: 1682-1692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation is associated with intracellular reactive oxygen species.2006

    • Author(s)
      Niiya Y , et. al.
    • Journal Title

      Brain Res 1108

      Pages: 179-187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Is regeneration of injured spinal cord by bone marrow stromal cells transplantation a "Mission Impossible"?2006

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

      Bunshi Keckan-Byou 5

      Pages: 436-442

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells2006

    • Author(s)
      Shichinohe H, Kuroda S, et al.
    • Journal Title

      J Nucl Med 47

      Pages: 486-491

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)2006

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

      Brain Res 1087

      Pages: 15-27

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation2006

    • Author(s)
      Niiya Y, Kuroda S, et al.
    • Journal Title

      Brain Res 1108

      Pages: 179-187

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bone marrow stromal cell transplantation preserves gamma-aminobutyric acid (GABA) receptor function in injured spinal cord2006

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

      J Neurotrauma 23

      Pages: 1682-1692

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cerebral oxygen metabolism and neuronal integrity in patients with impaired vasoreactivity due to occlusive carotid artery diseases2006

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

      Stroke 37

      Pages: 393-398

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical features of familial moyamoya disease2006

    • Author(s)
      Nanba R, Kuroda S, et al.
    • Journal Title

      Child Nerv Syst 22

      Pages: 258-262

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells : An autoradiographic and histologic analysis2006

    • Author(s)
      Shichinohe H, Kuroda S et al.
    • Journal Title

      J Nucl Med 47

      Pages: 1-6

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC) - A preliminary study using microarray analysis2006

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

      Brain Res (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuroprotective effect of a heat shock protein inducer, geranylgeranyl-acetone in permanent focal cerebral ischemia.2005

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

      Brain Res 1032

      Pages: 176-182

    • 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] In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.2005

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

      J Neurotrauma 22

      Pages: 907-918

    • 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] Do bone marrow stromal cells proliferate after transplantation into mice cerebral infarct?2005

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

      Brain Res 1065

      Pages: 60-67

    • 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] Neuroprotective effect of a heat shock protein inducer, geranylgeranyl-acetone in permanent focal cerebral ischemia.2005

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

      Brain Res 1032

      Pages: 176-182

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.2005

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

      J Neurotrauma 22

      Pages: 907-918

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Do bone marrow stromal cells proliferate after transplantation into mice cerebral infarct?2005

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

      Brain Res 1065

      Pages: 60-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A novel coating biomaterial for intracranial aneurysms: effects and safety in extra-and intracranial carotid artery.2005

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

      Neuropathology 25

      Pages: 66-76

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] In vivo fluorescence tracking of bone marrow stromal cells transplanted into rat spinal cord injury model.2005

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

      J Neurotrauma 22

      Pages: 907-918

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Do bone marrow stromal cells proliferate after transplantation into mice cerebral infarct?2005

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

      Brain Res 1065

      Pages: 60-67

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bone marrow stromal cells differentiate into neurons and promote axon elongation in spinal cord slice cultures: their role in cell transplantation therapy for spinal cord injury.

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

      Neurorehab and Neural Repair (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow stromal cell transplantation for spinal cord injury.

    • Author(s)
      Chiba Y , et. al.
    • Journal Title

      Rehabilitation Igaku (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow stromal cells differentiate into neurons and promote…

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

      Neurorehabil Neural Repair (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨髄間質細胞を用いた損傷脊髄の再生

    • Author(s)
      千葉泰弘
    • Journal Title

      リハビリテーション医学 (in press)

    • Related Report
      2007 Annual Research Report
  • [Presentation] 顆粒球コロニー刺激因子は骨髄間質細胞の移植効果を賦活する2008

    • Author(s)
      穂刈正昭
    • Organizer
      日本再生治療学会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨髄間質細胞の移植は損傷脊髄における皮質脊髄路の再生を促進する2008

    • Author(s)
      千葉泰弘
    • Organizer
      日本再生治療学会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨髄間質細胞の移植はびまん性脳損傷による高次脳機能障害を改善する2008

    • Author(s)
      丸一勝彦
    • Organizer
      日本再生治療学会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨髄間質細胞を用いた損傷脊髄の再生2007

    • Author(s)
      黒田 敏
    • Organizer
      日本リハビリテーション医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2007-06-06
    • Related Report
      2007 Annual Research Report
  • [Book] Annual Review 神経 20072007

    • Author(s)
      黒田 敏, ら
    • Total Pages
      336
    • Publisher
      中外医学者
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review Shinkei 20072007

    • Author(s)
      Kuroda S , et. al.
    • Total Pages
      336
    • Publisher
      Chugai Igaku Sha
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review神経2007

    • Author(s)
      黒田 敏
    • Total Pages
      450
    • Publisher
      骨髄間質細胞による中枢神経再生-最近の進歩
    • Related Report
      2007 Annual Research Report
  • [Book] Annual Review 神経 20072007

    • Author(s)
      黒田 敏, 岩崎喜信
    • Total Pages
      500
    • Publisher
      中外医学社
    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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