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Cell transplantation of Embryonic Stem Cells for Spinal Cord Injury

Research Project

Project/Area Number 19591695
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKASE Hiroyuki  Nara Medical University, 医学部, 准教授 (10217739)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Fumihiko  奈良県立医科大学, 医学部, 助教 (70433331)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2009: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords脊髄損傷 / 再生治療 / 胚芽幹細胞 / 基礎研究 / マウス / 補体活性抑制 / 脊髄血流
Research Abstract

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5×10-9M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplan … More ted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors. Less

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (10 results)

All 2009 2008 2007 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (4 results)

  • [Journal Article] Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement2009

    • Author(s)
      Toriumi H, Yoshikawa M, Matsuda R, Nishimura F, Yamada S, Hirabayashi H, Nakase H, Nonaka J, Ouji Y, Ishizaka S, Sakaki T
    • Journal Title

      Neural Res 31

      Pages: 220-227

    • Related Report
      2009 Final Research Report
  • [Journal Article] Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development2009

    • Author(s)
      Matsuda R, Yoshikawa M, Kimura H Ouji Y, Nakase H, Nishimura F, Nonaka J, Toriumi H, Yamada S Nishiofuku M, Moriya K, Ishizaka S Nakamura M, Sakaki T
    • Journal Title

      Cell Transplant 18

      Pages: 39-54

    • Related Report
      2009 Final Research Report
  • [Journal Article] Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development2009

    • Author(s)
      Matsuda R., Yoshikawa M., Kimura H., Ouji Y., Nakase H., Nishimura F., Nonaka J., Toriumi H., Yamada S., Nishiofuku M., Moriya K., Ishizaka S., Nakamura M., Sakaki T.
    • Journal Title

      Cell Transplant 18

      Pages: 39-54

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of Cl esterase inhibitor on acute traumatic spinal cord injury in rat.2008

    • Author(s)
      Tei R, Nakase H, Sakaki T
    • Journal Title

      Neurol Res 30(7)

      Pages: 761-7

    • Related Report
      2009 Final Research Report
  • [Journal Article] Protective effect of Cl esterase inhibitor on acute traumatic spinal cord injury in the rat.2008

    • Author(s)
      Tei R., Kaido T., Nakase H., Sakaki T.
    • Journal Title

      Neuro Res 30

      Pages: 761-767

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of Cl esterase inhibitor on acute traumatic spinal cord injury in the rat.

    • Author(s)
      Tei R
    • Journal Title

      Neurol Res. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 頚椎・頚髄損傷に対する外科的治療. ~当科での方針と治療成績~2009

    • Author(s)
      中瀬裕之, 竹島靖浩, 本山靖, 朴永銖, 平林秀裕, 榊寿右
    • Organizer
      第32回日本神経外傷学会
    • Place of Presentation
      下関
    • Year and Date
      2009-04-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 脊髄損傷に対するES細胞移植治療の問題点2008

    • Author(s)
      松田良介, 中瀬裕之, 木村新, 西村文彦, 吉川正英, 榊寿右
    • Organizer
      第23回日本脊髄外科学会
    • Place of Presentation
      宮城
    • Year and Date
      2008-06-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] Co-transplantation of ES cells and bone marrow stromal cells following spinal cord in jury supPresses tumordevelopment2007

    • Author(s)
      Matsuda R, Y, shikawa M, Kimura H, Ouji Y, Nakase H, Ishizaka S, Sakaki T
    • Organizer
      2007 Shanghai International Symposium on Stem Cell Research
    • Place of Presentation
      Shanghai
    • Year and Date
      2007-11-07
    • Related Report
      2009 Final Research Report
  • [Presentation] Co-transplalltation of ES cells and bone marrow stromal cells following spinal cord injury suppresses tumor develoment.2007

    • Author(s)
      Matsuda R
    • Organizer
      2007 Shanghai International Symposium on Stem Cell Research
    • Place of Presentation
      Shanghai
    • Year and Date
      2007-11-07
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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