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2004 Fiscal Year Final Research Report Summary

Establishment of adult rat-derived stem cells, and histological/functional reconstruction of spinal cord by auto- and allo-grafting of those stem cells

Research Project

Project/Area Number 15300114
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionKyoto University Graduate School of Medicine

Principal Investigator

IDE Chizuka  Kyoto University, Graduate School of Medicine, Department of Anatomy and Neurobiology, Professor, 医学研究科, 教授 (70010080)

Co-Investigator(Kenkyū-buntansha) SUZUKI Yoshihisa  Kyoto University, Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Associate Professor, 医学研究科, 助教授 (30243025)
DEZAWA Mari  Kyoto University, Graduate School of Medicine, Department of Anatomy and Neurobiology, Associate Professor, 医学研究科, 助教授 (50272323)
MATSUMOTO Naoya  Kyoto University, Graduate School of Medicine, Department of Anatomy and Neurobiology, Research Associate, 医学研究科, 助手 (50359808)
Project Period (FY) 2003 – 2004
Keywordsbone marrow stromal cell / neural stem cell / cell transplantation / spinal cord injury / astrocyte / choroid plexus ependymal cell / intra-cerebrospinal fluid injection / BBB scale
Research Abstract

Based on the early experiments, we recognized that there are big barriers for neural stem cells to be clinically applied : those are ethical problems concerning the use of fetus and inevitable allergenic transplantation. On the other hand, bone marrow stromal cells (BMSCs) have great advantages in being autogenic for clinical application. In experiments, BMSCs were injected into the cerebrospinal fluid (CSF) through the 4^th ventricle of the rat. Many injected BMSCs were attached to the spinal cord surface, and some of them further invaded the lesion. Based on the BBB scale, cell-graft rats showed 14 15 and 11 points in locomotion, while the controls were 10 and 8 points, in the mild and strong spinal cord crush, respectively. The size of spinal cord cavity was ca. 1/2 smaller in the cell-graft rats than the controls. Less proliferation of astrocytes was observed, and a larger amount of neural components was preserved in the cell-graft rats than in the controls.
Injected cells disappear … More ed from the spinal cord within 4-5 weeks after injection. This implies that injected BMSCs exerted their effects not by being integrated into the host tissue, but by releasing some trophic factors into the CSF. The in vitro experiments also supported this hypothesis. BMSCs function not as stem cells, but as ordinary somatic cells derived from adult animals. It is considered that BMSCs suppress the degenerative processes, and at the same time promote the survival, of injured cells at the early stage of degeneration. We confirmed the safety of BMSC injection into the CSF in the monkey by injecting autogenic BMSCs through lumbar puncture. We provided a complete protocol for clinical application, and the Ethic Committee of Kansai University approved this cell transplantation to patients with spinal cord therapy by BMSC transplantation to patients with spinal cord injury on July 1^<st> 2005. We are now ready for the BMSC transplantation therapy to patients matched to the protocol.
In parallel with this study, we also examined the effects of choroid plexus ependymal (epithelial) cells to the ischemic brain injury, and clarified that the injection of cultured choroid plexus ependymal cells have a great effect on the recovery of brain tissue from ischemic damages. This finding might open a new horizon for the therapy of ischemic brain injury. Less

  • Research Products

    (55 results)

All 2006 2005 2004 2003 Other

All Journal Article (51 results) Book (4 results)

  • [Journal Article] Choroid Plexus ependymal cells host neural progenitor cells in the rat.2006

    • Author(s)
      Itokazu Y., Ide C, et al.
    • Journal Title

      Glia 53

      Pages: 32-42

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 精髄再生研究の歩み2006

    • Author(s)
      井出千束
    • Journal Title

      藍野大学紀要 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Choroid plexus ependymal cells host neural progenitor cells in the rat.2006

    • Author(s)
      Itokazu Y., Ide C., et al.
    • Journal Title

      Glia 53

      Pages: 32-42

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Grafting of choroid plexus : clinical implications. In : Blood-Cerebrospinal Fluid Barrier (Eds; A. Chodobski and W. Zheng)2005

    • Author(s)
      Matsumoto N., Ide C., et al.
    • Journal Title

      Taylor & Francis, PP.

      Pages: 519-538

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neurogenesis in the ependymal layer of the adult 3rd ventricle.2005

    • Author(s)
      Xu Y., Ide C., et al.
    • Journal Title

      Exp, Neurol. 192

      Pages: 251-264

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Marrow stromal cells : implications in health and disease in the nervous system.2005

    • Author(s)
      Dezawa M., Ide C., et al.
    • Journal Title

      Curr. Mol. Med. 5

      Pages: 723-732

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bone marrow stromal cells generate muscle cells and repair muscle degeneration.2005

    • Author(s)
      Dezawa M., Ide C., et al.
    • Journal Title

      Science 309

      Pages: 314-317

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Conditioned medium of the primary culture of rat choroid plexus epithelial (modified ependymal) cells enhances neurite outgrowth and survival of hippocampal neurons.2005

    • Author(s)
      Watanabe Y., Ide C., et al.
    • Journal Title

      Neurosci. Lett. 379

      Pages: 158-163

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Survival of neural progenitor cells from subventricular sone of adult rat after transplantation into the host spinal cord of the same strain adult rat.2005

    • Author(s)
      Mligiliche N., Ide C., et al.
    • Journal Title

      Anat. Sci. Int. 80

      Pages: 229-234

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 特集「末梢神経と脊髄の再生メカニズム」の巻頭言 : 再生から見た末梢神経と脊髄2005

    • Author(s)
      井出千束
    • Journal Title

      細胞 37

      Pages: 214-215

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 脳脊髄液経由細胞移植法による脊髄損傷治療2005

    • Author(s)
      太田正佳, 鈴木義久, 井出千束
    • Journal Title

      細胞 37

      Pages: 228-230

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 神経再生医学の将来と倫理 脊髄の再生メカニズムをライフワークとして2005

    • Author(s)
      井出千束
    • Journal Title

      医療と社会 97

      Pages: 1-4

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 末梢神経の再生から脊髄の再生へ2005

    • Author(s)
      井出千束
    • Journal Title

      ミクロスコピア 22

      Pages: 175-181

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neurogenesis in the ependymal layer of the adult 3^rd ventride.2005

    • Author(s)
      Xu Y., Ide C., et al.
    • Journal Title

      Exp.Nerurol. 192

      Pages: 251-264

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Marrow stromal cells : implications in health and disease in the nervous system.2005

    • Author(s)
      Dezawa M., Ide C., et al.
    • Journal Title

      Curr.Mol.Med. 5

      Pages: 723-732

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Conditioned medium of the primary culture of rat choroid plexus epithelial (modified ependylnal) cells enhances neurite outgrowth and survival of hippocampal neurons.2005

    • Author(s)
      Watanabe Y., Ide C., et al.
    • Journal Title

      Neurosci.Lett. 379

      Pages: 158-163

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Survival of neural progenitor cells from subventricular zone of adult rat after transplantation into the host spinal cord of the same strain adult rat.2005

    • Author(s)
      Mligiliche N.L., Ide C., et al.
    • Journal Title

      Anat.Sci.Int. 80

      Pages: 229-234

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Implantation of neural stem cells via cerebrospinal fluid into the injured dorsal root.2004

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      Neuroreport 15

      Pages: 1249-1253

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes.2004

    • Author(s)
      Kinoshita N., Ide C., et al.
    • Journal Title

      Genes Cells 9

      Pages: 1-14

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alginate enhances elongation of early regenerating axons in spinal cord of young rats.2004

    • Author(s)
      Kataoka K., Ide C., et al.
    • Journal Title

      Tissue Engineering 10

      Pages: 493-504

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation.2004

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      Exp. Neurol. 187

      Pages: 266-278

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel alginate-heparin gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve.2004

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      J. Biomed. Mater. Res. 71A

      Pages: 661-668

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Specific induction of neuronal cells from bone-marrow stromal cells and application for autologous transplantation.2004

    • Author(s)
      Dezwa M., Ide C., et al.
    • Journal Title

      J. Clin. Invest. 113

      Pages: 1701-1710

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro.2004

    • Author(s)
      Kimura K., Ide C., et al.
    • Journal Title

      J. Neurocytol. 33

      Pages: 465-476

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astroccytes.2004

    • Author(s)
      Kinoshita N., Ide C., et al.
    • Journal Title

      Genes Cells 9

      Pages: 1-14

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation.2004

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      Exp.Neurol. 187

      Pages: 266-278

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel alginate-heparin gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve.2004

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      J.Biomed Mater.Res. 71A

      Pages: 662-668

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific induction of neuronal cells from bone-marrow stromal cells and application for autologous transplantation.2004

    • Author(s)
      Dezawa M., Ide C., et al.
    • Journal Title

      J.Clin.Invest. 113

      Pages: 1701-1710

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro.2004

    • Author(s)
      Kimura K., Ide C., et al.
    • Journal Title

      J.Neurocytol. 33

      Pages: 465-476

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat.2003

    • Author(s)
      Bali H., Ide C., et al.
    • Journal Title

      J. Neurosci. Method. 124

      Pages: 181-187

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bone marrow stromal cells enhance differentiation of co-cultured neurosphere cells and promote regeneration of injured spinal cord.2003

    • Author(s)
      Wu S., Ide C., et al.
    • Journal Title

      J. Neurosci. Res. 72

      Pages: 343-351

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Isolation of neural stem cells from forebrain of deceased early postnatal and adult rats with protracted postmortem intervals.2003

    • Author(s)
      Xu Y., Ide C., et al.
    • Journal Title

      J. Neurosci. Res. 74

      Pages: 533-540

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Isolation of a set of genes expressed in the choroid plexus of the mouse using suppression subtractive hybridization.2003

    • Author(s)
      Matsumoto N., Ide C., et al.
    • Journal Title

      Neuroscience 117

      Pages: 405-415

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Poly lactic acid-caprolactone copolymer tube with a denatured skeletal muscle segment inside as a guide for peripheral nerve refeneration : a morphological and electrophysiological evaluation of the regenerated nerves.2003

    • Author(s)
      Mligiliche N.L., Ide C., et al.
    • Journal Title

      Anat. Sci. Int. 78

      Pages: 156-161

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 脊髄再生の可能性2003

    • Author(s)
      井出千束
    • Journal Title

      Brain and Spinal Cord 10

      Pages: 1-3

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat.2003

    • Author(s)
      Bai H., Ide C., et al.
    • Journal Title

      J.Neurosci.Method. 124

      Pages: 181-187

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Bone marrow stromal cells enhance differentiation of co-cultured neurosphere cells and promote regeneration of injured spinal cord.2003

    • Author(s)
      Wu S., Ide C., et al.
    • Journal Title

      J.Neurosci.Res. 72

      Pages: 343-351

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Isolation of neural stem cells from forebrain of deceased early postnatal and adult rats with protracted postmortem intervals.2003

    • Author(s)
      Xu Y., Ide C., et al.
    • Journal Title

      J.Neurosci.Res. 74

      Pages: 533-540

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Poly lactic acid-caprolactone copolymer tube with a denatured skeletal muscle segment inside as a guide for peripheral nerve regeneration : a morphological and electrophysiological evaluation of the regenerated nerves.2003

    • Author(s)
      Mligiliche N.L., Ide C., et al.
    • Journal Title

      Anat.Sci Int. 78

      Pages: 156-161

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increase in bFGF-responsive neural progenitor population forllowing contusion injury of the adult rodent spinal cord.

    • Author(s)
      Xu Y., Ide C., et al.
    • Journal Title

      Nerosci. Lett. (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Concepts of cell transplantation for spinal cord injury - a short overview -

    • Author(s)
      Ide C.
    • Journal Title

      Aino Journal (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regeneration (synopsis)

    • Author(s)
      Ide C., et al.
    • Journal Title

      Encyclopedic Reference of Neuroscience (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The role of basal lamina in nerve regeneration.

    • Author(s)
      Ide C.
    • Journal Title

      Encyclopedic Reference in Neuroscience (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The possible grafting of nerve segments dissected from human cadavers - a preliminary report.

    • Author(s)
      Fujimoto E., Ide C., et al.
    • Journal Title

      Anat. Sci. Int. (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Transplantation of bone marrow stromal cells for nerve regeneration in CNS.

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      Encyclopedic Reference in Neuroscience (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Increase in bFGF-responsive neural progenitor population following contusion injury of the adult rodent spinal cord.

    • Author(s)
      Xu Y., Ide C., et al.
    • Journal Title

      Neurosci.Lett. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Concepts of cell transplantation for spinal cord injury-a short overview-

    • Author(s)
      Ide C.
    • Journal Title

      Aino Journal (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regeneration (synopsis).

    • Author(s)
      Ide C., Dezawa M., et al.
    • Journal Title

      Encyclopedic Reference of Neuroscience (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The role of basal lamina in nerve regeneration.

    • Author(s)
      Ide C.
    • Journal Title

      Encyclopedic Reference of Neuroscience (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The possible grafting of nerve segments dissected from human cadavers-a preliminary report.

    • Author(s)
      Fujimoto E., Ide C., et al.
    • Journal Title

      Anat.Sci Int. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transplantation of bone marrow stromal cells for nerve regeneration in CNS.

    • Author(s)
      Ohta M., Ide C., et al.
    • Journal Title

      Encyclopedic Reference of Neuroscience (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 医学書院2006

    • Author(s)
      井出千束
    • Publisher
      細胞外基質 標準細胞生物学(教科書)分担執筆(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 西村書店2006

    • Author(s)
      井出千束(共編著)
    • Publisher
      電子組織学図譜-解説付き-(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 西村書店2006

    • Author(s)
      井出千束(共訳)
    • Publisher
      臨床神経解剖学(フィッツジェラルド、フォラン・クラン共著)サンダーズ(Clinical Neuroanatomy, M.J.T. FitzGerald and Jean Folan-Curran, W.B.Saunders)(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Grafting of choroid plexus : clinical implications. Blood-Cerebrospinal Fluid Barrier (Eds ; A.Chodobski and W.Zheng)2005

    • Author(s)
      Matsumoto N., Ide C., et al.
    • Total Pages
      519-538
    • Publisher
      Taylor & Francis
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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