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Development of new regenerative therapy for central nerve system using the conditioned media derived from human dental pulp stem cells

Research Project

Project/Area Number 23659914
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Dental engineering/Regenerative dentistry
Research InstitutionNagoya University

Principal Investigator

UEDA Minoru  名古屋大学, 医学系研究科, 教授 (00151803)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Akihito  名古屋大学, 大学院・医学系研究科, 准教授 (50244083)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsヒト歯髄幹細胞 / 培養上清 / 脊髄損傷 / 難治性中枢神経系疾患 / 神経再生 / 歯髄幹細胞 / ミクログリア / 抗炎症
Research Abstract

We found that conditioned medium (CM) from stem cells derived from human exfoliated deciduous teeth (SHED), administered intrathecally into the severely injured adult rat SC, resulted in marked functional recovery. SHED-CM treatment inhibited SCI-induced apoptosis, preserved neural fibers and myelin sheaths, and promoted descending serotonergic raphespinal axon growth. Importantly, these pathophysiological recoveries were supported by a remarkable immunoregulatory function of SHED-CM, which converted the pro-inflammatory SCI conditions to a tissue repair/regenerating platform by modulating the microglia/macrophage phenotype. SHED-CM directly induced IL-10-producing M2 microglia synergistically with a major glial-scar extracellular matrix component, chondroitin sulphate proteoglycan, in vitro. Thus, SHED-CM may enable new stem-cell-based regenerative therapies for SCI that do not involve cell transplantation.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (11 results)

All 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (4 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice2013

    • Author(s)
      M. Yamagata, A. Yamamoto, E. Kako, N. Kaneko, K. Matsubara, K. Sakai, K. Sawamoto and M. Ueda
    • Journal Title

      Stroke

      Volume: Vol.44, No.2 Pages: 551-554

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice2013

    • Author(s)
      Yamagata Mari
    • Journal Title

      Stroke

      Volume: 44 Issue: 2 Pages: 551-554

    • DOI

      10.1161/strokeaha.112.676759

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Dental Pulp-Derived Stem Cells Promote Locomotor Recovery after Complete Transection of the Rat Spinal Cord by Multiple Neuro-Regenerative Mechanisms2012

    • Author(s)
      K. Sakai, A. Yamamoto, K. Matsubara, S. Nakamura, M. Naruse, M. Yamagata, K. Sakamoto, R. Tauchi, N. Wakao, S. Imagama, H. Hibi, K. Kadomatsu, N. Ishiguro, and M. Ueda
    • Journal Title

      The Journal of Clinical Investigation

      Volume: Vol.122, No.1 Pages: 80-90

    • NAID

      120005951941

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multifaceted neuro-regenerative activities of human dental pulp stem cells promote locomotor recovery after complete transection of the rat spinal cord2012

    • Author(s)
      Kiyoshi Sakai, Akihito Yamamoto#, Kohki Matsubara, Shoko Nakamura, Mami Naruse (#correspondence)
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 122 Pages: 80-90

    • DOI

      10.1172/jci59251

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト歯髄幹細胞由来無血清培養上清を応用した急性期脊髄損傷治療と治癒メカニズムの解析2012

    • Author(s)
      松原弘記,山本朗仁,酒井陽,野田万里子, 松下嘉泰,錫村明生, 上田実
    • Organizer
      第11回日本再生医療学会総会・学術大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒト歯髄幹細胞由来液性因子を応用した急性期脊髄損傷治療2012

    • Author(s)
      松原弘記,山本朗仁,酒井陽,松下嘉泰,上田実
    • Organizer
      第57回日本口腔外科学会総会・学術大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒ ト歯髄幹細胞由来無血清培養上清を応用 した急性期脊髄損傷治療と治癒メカニズ ムの解析2012

    • Author(s)
      松原 弘記
    • Organizer
      第 11 回日本再生医療学会 総会・学術大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト歯髄幹細胞由来液性因子 を応用した急性期脊髄損傷治療2012

    • Author(s)
      松原 弘記
    • Organizer
      第57 回日本口腔外科学会総会・学術大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Book] 歯学系 再生医療叢書2012

    • Author(s)
      上田実、他
    • Publisher
      朝倉書店
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 組織再生ミクログリア・マクロファージ誘導型抗炎症製剤2013

    • Filing Date
      2013-02-13
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 組織再生ミクログリア・マ クロファージ誘導型抗炎症製剤2013

    • Inventor(s)
      山本朗仁、上田実、松原弘記
    • Industrial Property Rights Holder
      山本朗仁、上田実、松原弘記
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-02-13
    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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