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2006 Fiscal Year Final Research Report Summary

neural stem cell transplantation for the Parkinson's disease

Research Project

Project/Area Number 15591525
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

SUGIU Kenji  OKAYAMA UNIVERSITY, HOSPITALS, LECTURER, 医学部・歯学部附属病院, 講師 (40325105)

Co-Investigator(Kenkyū-buntansha) DATE Isao  OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, PROFESSOR, 医学部・歯学部附属病院, 教授 (70236785)
TOKUNAGA Kouji  OKAYAMA UNIVERSITY, HOSPITALS, LECTURER, 医学部・歯学部附属病院, 講師 (40294467)
MIYOSHI Yasuyuki  OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, LECTURER, 大学院医歯薬学総合研究科, 講師 (00362997)
ONODA Keisuke  OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, ASSISTANT, 大学院医歯薬学総合研究科, 助手 (20379837)
MATSUI Toshihiro  OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE DENTISTRY AND PHARMACEUTICAL SCIENCES, ASSISTANT, 大学院医歯薬学総合研究科, 助手 (80362995)
Project Period (FY) 2003 – 2006
Keywordsadult / tyrosine hydroxylase / dopamine / GDNF / neurotrophic factor / microenvironment / CREB / differentiation
Research Abstract

For Parkinson's disease (PD) to realize intracerebral cell replacement therapy using neural stem cells, we hypothesized that autologous transplantation using neural stem cells (NSCs) is one of the safest and most useful therapies.
We showed the following:
First, neural stem cells were harvested from the subventricular zone of adult rodents or primates, were expanded to the transplantable number of cells in the presence of proliferating factors, and could be differentiated into a large number of dopaminergic neurons using tyrosine hydroxylase-inducing factor.
Second, transplantation of adult NSCs had the neuroprotective effects as the behavioral and histological improvements. The mechanism is that adult NSCs could secrete the various kinds of neurotrophic factors and cytokines (GDNF, EPO, CNTF etc), which had the effects surrounding to the transplanted striatum.
Third, We established the GDNF, which has a one of the most neurotrophic effect on the dopaminergic neurons, producing NSCs (NSC-G … More DNF) using GDNF gene transfection method. The transplantation of NSC-GDNF had a neuroprotective effect in the parkinsonian model animals as the behavioral and histological improvements. GDNF secreted from NSC-GDNF also had a strong surviving and migrating effect for the grafted cells and migrating. The mechanism is that NSC-GDNF transplantation may change the microenvironment into the lesioned striatum and the accommodated host glial cells may release the other trophic factors except for GDNF.
Finally, transplantation of dopaminergic (DA) neurons derived from adult NSCs has a restorative effect for the parkinsonian rat model. The survival of the grafted DA neurons derived from NSCs was poor in the lesioned striatum, but the great number of synapse formation between the grafted DA neurons and host neurons were observed. The mechanism is that upregulation of BDNF and phosphorylated CREB may enhance the synaptogenesis.
These results suggested that autologous transplantation of adult neural stem cells is useful in the treatment of PD. Less

  • Research Products

    (8 results)

All 2006 2004

All Journal Article (8 results)

  • [Journal Article] The high integration and differentiation potential of autologous neural stem cell transplantation compared with allogeneic transplantation in adult rat hippocampus2006

    • Author(s)
      Muraoka K
    • Journal Title

      Experimental Neurology 1999・2

      Pages: 311-327

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ex vivo gene therapy : transplantation of neurotrophic factor-secreting cells for cerebral ischemia2006

    • Author(s)
      Yasuhara T
    • Journal Title

      Frontiers in Bioscience 11

      Pages: 760-775

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Control of dopamine-secretion by Tet-Off system in an in vivo model of Parkinsonian rat2006

    • Author(s)
      Kobayashi K
    • Journal Title

      Bain Research 1102

      Pages: 1-11

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neuroprotection and repair by using adult-derived neural stem cell grafting for neurological disorders2006

    • Author(s)
      Date I
    • Journal Title

      Minimally Invasive Neurosurgery and Multidisciplinary

      Pages: 131-137

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The high integration and differentiation potential of autologous neural stem cell transplantation compared with allogeneic transplantation in adult rat hippocampus2006

    • Author(s)
      Muraoka K
    • Journal Title

      Experimental Neurology 1999-2

      Pages: 311-327

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ex vivo gene therapy : transplantation of Neurotrophic factor-secreting cells for cerebral ischemia2006

    • Author(s)
      Yasuhara T
    • Journal Title

      Frontiers in Bioscience 11

      Pages: 760-775

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rebleeding of a vertebral artery dissecting aneurysm during sten t-assisted coil embolization : A pitfall of "stent and coil" tec hnique2004

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

      Surgical Neurology 61

      Pages: 365-370

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Rebleeding of a vertebral artery dissecting aneurysm during stent-assisted coil embolization : A pitfall of "stent and coil" technique2004

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

      Surgical Neurology 61

      Pages: 365-370

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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