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Development of new gel used for artificial nerve to differenciate neural stem cells and to promote elongation ofaxons in damaged peripheral and central nervous system

Research Project

Project/Area Number 14207073
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionKyoto University

Principal Investigator

SUZUKI Yoshihisa  Kyoto Univ., Grad.School of Med., Dept.of Plast. & Reconstr.Surg., Assoc., Prof., 医学研究科, 助教授 (30243025)

Co-Investigator(Kenkyū-buntansha) IDE Chizuka  Kyoto Univ., Grad.School of Med., Dept.of Anat. & Neuro Biol., Prof., 医学研究科, 教授 (70010080)
TANIHARA Masao  Nara Institute of Science and Technology, Grad.School of Matel Sci., Prof., 物質創成科学研究所, 教授 (50294286)
NAKATANI Toshio  Kanasai Medical Univ., Dept.of Emargency medicine., Prof., 医学部, 教授 (70188978)
遠藤 克昭  京都大学, 医学研究科, 助手 (30025613)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥50,440,000 (Direct Cost: ¥38,800,000、Indirect Cost: ¥11,640,000)
Fiscal Year 2004: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2003: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2002: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Keywordsneural stem cell / cerebrospinal fluid / spinal cord injury / regeneration / transplantation / 構造多糖類 / 再生医療 / ラット / 末梢神経 / 中枢神経 / マトリクス / 吸収性材料 / アストロサイト / オリゴデンドロサイト / 分化 / 損傷 / 脊髄 / アルギン酸
Research Abstract

Transplantation of neural stem cells has been studied extensively for the treatment of central nervous system(CNS) injury (Seaberg and van-der-Kooy,2002;Van-der-Kooy and Weiss, 2000;Fuchs and Segre,2000). There have been various approaches to transplantation, including direct local administration by injection with or without artificial substrates as cell carriers (Wu et al.,2001) into the injured brain (Fricker et al.,1999;Gage et al.,1995) and spinal cord (Akiyama et al.,2001). On the other hand, gene therapeutic agents (Bajocchi et al.,1993), neurotrophic factors (Araujo and Hilt,1997) and drugs such as nitecapone (Mannisto et al.,1992) have been administered through the CSF.
We examined the distribution of hippocampus-derived neural stem cells on the spinal cord surface for up to 3 weeks following injection through the 4th ventricle. The injected cells were disseminated as tiny spots on the pia mater of the spinal cord and proliferated into large cell-clusters. On both the dorsal and … More ventral side, cell clusters increased in number rapidly up to 5 days after injection, and thereafter decreased gradually due to the coalition of neighbouring clusters. Concomitantly, individual cell clusters continuously increased in size, occupying almost 50% of the spinal cord surface. Cell attachment was usually found around blood vessels, along which cells invaded into the spinal cord. In the injured site, cells migrated into the lesion and were integrated into the spinal cord tissue, some of which had differentiated into astrocytes 1-2 weeks after injection. BrdU-uptake experiments demonstrated that the transplanted cells proliferated within the host cerebrospinal fruid.
These results indicate that application of neural stem cells through the ventricle is a unique method to disseminate cells all over the spinal cord, and that they can migrate and be integrated into the injured spinal cord.
Transplantation of neural stem cells has been studied extensively for the treatment of central nervous system(CNS) injury (Seaberg and van-der-Kooy,2002;Van-der-Kooy and Weiss, 2000;Fuchs and Segre,2000). There have been various approaches to transplantation, including direct local administration by injection with or without artificial substrates as cell carriers (Wu et al.,2001) into the injured brain (Fricker et al.,1999;Gage et al.,1995) and spinal cord (Akiyama et al.,2001). On the other hand, gene therapeutic agents (Bajocchi et al.,1993), neurotrophic factors (Araujo and Hilt,1997) and drugs such as nitecapone (Mannisto et al.,1992) have been administered through the CSF. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (27 results)

All 2005 2004 2003 2002 Other

All Journal Article (20 results) Publications (7 results)

  • [Journal Article] Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells.2005

    • Author(s)
      Saito A., Suzuki Y., et al.
    • Journal Title

      Journal of Biomed.Mater.Res. 72A

      Pages: 77-82

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells.2005

    • Author(s)
      Saito A., Suzuki Y., Ogata S., Ohtsuki C., Tanihara M.
    • Journal Title

      J Biomed.Mater.Res. 72A

      Pages: 77-82

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Alginate Enhances Elongation of Early Regenerating Axons in Spainal Cord of Young Rats.2004

    • Author(s)
      Kataoka K., Suzuki, Y., et al.
    • Journal Title

      Tissue Engineering 10(3/4)

      Pages: 493-504

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

    • Author(s)
      Ohta M., Suzuki, Y., et al.
    • Journal Title

      Journal of Biomed.Mater.Res. 71A

      Pages: 661-668

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

    • Author(s)
      Ohta M., Suzuki, Y., et al.
    • Journal Title

      NeuroReport. 15(8)

      Pages: 1249-1253

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.2004

    • Author(s)
      Saito A., Suzuki, Y., et al.
    • Journal Title

      Journal of Biomed.Mater.Res. 70A

      Pages: 115-121

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of alginate wound dressings linked with hybrid peptides derived from laminin and elastin.2004

    • Author(s)
      Hashimoto T., Suzuki, Y., et al.
    • Journal Title

      Biamaterials 25

      Pages: 1407-1414

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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., Suzuki, Y., et al.
    • Journal Title

      Experimental Neurology 187

      Pages: 266-278

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Alginate Enhances Elongation of Early Regenerating Axons in Spainal Cord of Young Rats.2004

    • Author(s)
      Kataoka K., Suzuki Y., Kitada M., Hashimoto T., Chou H., Bai H., Ohta M., Wu S., Suzuki K., Ide C.
    • Journal Title

      Tissue Engineering 10(3/4)

      Pages: 493-504

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

    • Author(s)
      Ohta M., Suzuki Y., Chou H., Ishikawa N., Suzuki S., Tanihara M., Suzuki Y., Mizushima Y., Dezawa M., Ide C.
    • Journal Title

      J Biomed.Mater.Res. 71A

      Pages: 661-668

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

    • Author(s)
      Ohta M., Suzuki Y., Noda T., Kataoka K., Chou H., Ishikawa N., Kitada M., Matsumoto N., Dezawa M., Ide C.
    • Journal Title

      Neuro Report 15(8)

      Pages: 1249-1253

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.2004

    • Author(s)
      Saito A., Suzuki Y., Ogata S., Otsuki C., Tanihara M.
    • Journal Title

      J Biomed.Mater.Res. 70A

      Pages: 115-121

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of alginate wound dressings linked with hybrid peptides derived from laminin and elastin.2004

    • Author(s)
      Hashimoto T., Suzuki Y., Tanihara M., Kakimaru Y., Suzuki K.
    • Journal Title

      Biomaterials 25

      Pages: 1407-1414

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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., Suzuki Y., Noda T., Ejiri Y., Dezawa M., Kataoka K., Chou H., Ishikawa N., Matsumoto N., Iwashita Y., Mizuta E., Kuno S., Ide C.
    • Journal Title

      Experimental Neurology 187

      Pages: 266-278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope.2003

    • Author(s)
      Saito A., Suzuki Y., et al.
    • Journal Title

      Biochemica et Biophysica Acta 1651

      Pages: 60-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat : a method for cell transplantation.2003

    • Author(s)
      Bai H., Suzuki Y., et al.
    • Journal Title

      Journal of Neuroscience Methods 124

      Pages: 181-187

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope.2003

    • Author(s)
      Saito A., Suzuki Y., Ogata S., Ohtsuki C., Tanihara M.
    • Journal Title

      Biochemica et Biophysica Acta 1651

      Pages: 60-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat : a method for cell transplantation.2003

    • Author(s)
      Bai H., Suzuki Y., Noda T., Wu S., Kataoka K., Kitada M., Ohta M., Chou H., Ide C.
    • Journal Title

      J Neuroscience Methods 124

      Pages: 181-187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Peripheral nerve regeneration through alginate gel : analysis of early outgrowth and late increase in diameter of regenerating axons.2002

    • Author(s)
      Hashimoto T., Suzuki, Y., et al.
    • Journal Title

      Exp.Brain Res. 146

      Pages: 356-368

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Peripheral nerve regeneration through alginate gel : analysis of early outgrowth and late increase in diameter of regenerating axons.2002

    • Author(s)
      Hashimoto T., Suzuki Y., Kitada M., Kataoka K., Wu S., Suzuki K., Endo K., Nishimura Y., Ide C.
    • Journal Title

      Exp.Brain Res. 146

      Pages: 356-368

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ohta, M.: "Bone marrow stromal cells infused into cerebrospainal fluid promote functional recovery of injured rat spinal cord with reduced cavity formation."Experimental Neurology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Hashimoto, T.: "Development of alginate wound dressings links with hybrid peptides delived from laminine and elastin."Biomaterials. 25. 1407-1414 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bai, H.: "Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fouth ventricle of the rat."Journal of Neuroscience Method. 124. 181-187 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wu Sufan: "Bone marrow stromal cells enhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord"Journal of Neuroscience Research. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Bai H.: "Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat : A method for cell transplantation"Journal of Neuroscience Methods. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashimoto T.: "Peripheral neural regeneration through gel-analysis of early outgrowth an increase in diameter of regenerated axons"Experimental Brain Research. 146. 356-368 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wu Sufan: "Immunohistochemical and electron microscopic study of invasion and differentiation in spinal cord lesion of neural stem cells grafted through CSF in rat"Journal of Neuroscience Research. 69. 940-945 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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