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RESEARCH FOR BONE MARROW STROMAL CELLS (BMSC) TRANSPLANTATION THERAPY FOR INJURED CENTRAL NERVOUS SYSTEM USING BIOMATERIALS AND GENE ANALYSIS

Research Project

Project/Area Number 15390426
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

IWASAKI Yoshinobu  HOKKAIDO UNIV., GRADUATE SCHOOL OF MED NEUROSURGERY, PROFESSOR, 大学院・医学研究科, 教授 (00113522)

Co-Investigator(Kenkyū-buntansha) KURODA Satoshi  HOKKAIDO UNIV., HOKKAIDO UNIV.HOSPITAL, NEUROSURGERY, LECTURER, 講師 (10301904)
SHICHINOHE Hideo  HOKKAIDO UNIV., HOKKAIDO UNIV.HOSPITAL, NEUROSURGERY, POST-DOCTORAL STAFF, 医員 (80374479)
HIDA Kazutoshi  HOKKAIDO UNIV., GRADUATE SCHOOL OF MED NEUROSURGERY, ASSISTANT PROFESSOR, 大学院・医学研究科, 助教授 (10238305)
YANO Shunsuke  HOKKAIDO UNIV., INSTITUTE FOR GENETIC MEDICINE, INSTRUCTOR, 助手 (20374481)
TAMURA Mamoru  HOKKAIDO UNIV., INSTITUTE FOR ELECTRIC SCIENCE, PROFESSOR, 電子科学研究所, 教授 (80089888)
小林 浩之  北海道大学, 大学病院, 医員 (70374478)
関 俊隆  北海道大学, 医学部・歯学部付属病院, 医員
池田 潤  北海道大学, 医学部・歯学部付属病院, 助手 (70332468)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsCerebral infarction / Spinal cord injury / Bone marrow stromal cells / Transplantation / Differentiation / Migration / Biomaterial / Neuroprotection / Regeneration / bone marrow / stromal cell / central nervous system / cerebral infarct / spinal cord injury / transplantation / differentiation
Research Abstract

We have established the culture system of the bone marrow stromal cells (BMSC) obtained from the rats and mice, and transplanted them into the animals subjected to cerebral infarction or spinal cord injury. These data were published in Neuropathology (2003) and Brain Res Protoc (2004). We isolated the BMSC from the green fluorescence protein (GFP)-transgenic mice and transplanted them into the mice subjected to cerebral infarction or spinal cord injury. We could visualize the transplanted cells through the skull or the dura mater in the living animals, using a novel fluorescence imaging technique. These data were published in Brain Res Protoc (2004) and 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 (in press). We also found that the BMSC actively repeat cell proliferation when transplanted into infarct brain, and published the data in Brain Res (2005). In addition, 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 organotypic spinal cord slice culture and a novel "in vitro transplantation" model. The data have been submitted to J Neurosurg. 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)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (23 results)

All 2006 2005 2004 2003 Other

All Journal Article (18 results) Publications (5 results)

  • [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(和文)」より
    • Related Report
      2005 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 (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 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
      2005 Annual Research Report 2005 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 (e-pub)(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 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 (in press)

    • Related Report
      2005 Annual Research Report
  • [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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 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

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [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

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] A pre-clinical assessment model of rat autogeneic bone marrow stromal cell transplantation into the central nervous system.2004

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

      Brain Res Protoc 14

      Pages: 37-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo tracking of bone marrow stromal cells transplanted into mice cerebral infarct by fluorescence optical imaging.2004

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

      Brain Res Protoc 13

      Pages: 166-175

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A pre-clinical assessment model of rat autogeneic bone marrow stromal cell transplantation into the central nervous system.2004

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

      Brain Res Protoc 14

      Pages: 37-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo tracking of bone marrow stromal cells transplanted into mice cerebral infarct by fluorescence optical imaging.2004

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

      Brain Res Protoc 13

      Pages: 166-175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] A pre-clinical assessment model of rat autogeneic bone marrow stromal cell transplantation into the central nervous system.2004

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

      Brain Res Protoc 14

      Pages: 37-44

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice2003

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

      Neuropathology 23

      Pages: 167-178

    • NAID

      50000315712

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice2003

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

      Neuropathology 23

      Pages: 167-178

    • NAID

      50000315712

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 中枢神経再生研究の最近の動向2003

    • Author(s)
      黒田 敏 他
    • Journal Title

      脊椎脊髄ジャーナル 16

      Pages: 96-100

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In Vivo Fluorescence Tracking of Bone Marrow Stromal Cells Transplanted into Rat Spinal Cord Injury Model

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

      J Neurotrauma (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Lee J B, Iwasaki Y, et al.: "Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice"Neuropathology. 23. 167-178 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Qiao F, Iwasaki Y, et al.: "Source localization of the re-build up phenomenon in pediatric moyamoya disease-a dipole distribution analysis using MEG and SPECT"Child's Nerv Syst. 19. 760-764 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shichinohe H, Iwasaki Y, et al.: "FK506 reduces infarct volume due to permanent focal cerebral ischemia by maintaining BAD turnover and inhibiting cytochrome c release"Brain Res. 1001. 51-59 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuroda S, Iwasaki Y, et al.: "Reduced blood flow and preserved vasoreactivity characterize oxygen hypometabolism dueto incomplete infarction in occlusive carotid artery diseases"J Nucl Med. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuroda S, Iwasaki Y, et al.: "Pretreatment and post-treatment evaluation of hemodynamic and metabolic parameters in intracranial dural arteriovenous fistulas with cortical venous reflux"Neurosurgery. (in press).

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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