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Development of regenerative therapy against severe peripheral nerve injury with a novel anti-inflammatory M2 macrophages inducer derived from dental pulp stem cells

Research Project

Project/Area Number 26293427
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokushima (2016-2017)
Nagoya University (2014-2015)

Principal Investigator

YAMAMOTO Akihito  徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (50244083)

Co-Investigator(Kenkyū-buntansha) 伊佐 正  生理学研究所, 発達生理学研究系認知行動発達機構研究部門, 教授 (20212805)
上田 実  名古屋大学, 医学(系)研究科(研究院), 教授 (00151803)
Research Collaborator KANO Fumiya  
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords歯髄幹細胞 / 末梢神経再生 / 顔面神経 / MCP-1 / sSiglec-9 / マクロファージ / シュワン細胞 / 歯学 / 再生医学 / 脳神経疾患 / 神経再生 / 炎症制御 / 瘢痕形成抑制
Outline of Final Research Achievements

We show that an implantation of the serum‐free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED‐CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. SHED‐CM specifically depleted of a set of anti‐inflammatory M2 macrophage inducers, monocyte chemoattractant protein‐1 (MCP‐1) and the secreted ectodomain of sialic acid‐binding Ig‐like lectin‐9 (sSiglec‐9) lost the ability to restore neurological function in this model. Notably, the implantation of a collagen graft containing MCP‐1/sSiglec‐9 into the nerve gap induced anti‐inflammatory M2 macrophage polarization, generated a Schwann‐cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. Taken together, our data suggest that MCP‐1/sSiglec‐9 regenerates PNs by inducing tissue‐repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (11 results)

All 2017 2015

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity2017

    • Author(s)
      Kano, F. Matsubara, K. Ueda, M. Hibi, H. Yamamoto, A.
    • Journal Title

      Stem Cells

      Volume: 3 Issue: 3 Pages: 641-653

    • DOI

      10.1002/stem.2534

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Conditioned media from hypoxic-cultured human dental pulp cells promotes bone healing during distraction osteogenesis2015

    • Author(s)
      Fujio M, Xing Z, Sharabi N, Xue Y, Yamamoto A, Hibi H, Ueda M, Fristad I, Mustafa K
    • Journal Title

      Journal of Tissue Engineering and Regenerative Medicine

      Volume: Epub ahead of print Issue: 7 Pages: 230-240

    • DOI

      10.1002/term.2109

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity2015

    • Author(s)
      Kohki Matsubara, Yoshihiro Matsushita, Kiyoshi Sakai, Fumiya Kano, Megumi Kondo, Mariko Noda, Noboru Hashimoto, Shiro Imagama, Naoki Ishiguro, Akio Suzumura, Minoru Ueda, Koichi Furukawa, Akihito Yamamoto
    • Journal Title

      Journal of Neuroscience

      Volume: 35 Issue: 6 Pages: 2452-2464

    • DOI

      10.1523/jneurosci.4088-14.2015

    • NAID

      120005946848

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Immunomodulatory function of DPSC secretome: lesson from nerve-injury diseases2017

    • Author(s)
      Akihito Yamamoto
    • Organizer
      2017 IADR/AADR/CADR General Session & Exhibition
    • Place of Presentation
      San Francisco, Calif., USA.
    • Year and Date
      2017-03-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯髄幹細胞由来の無血清培養上清を用いた再生医療2015

    • Author(s)
      山本朗仁
    • Organizer
      第60回日本口腔外科学会
    • Place of Presentation
      愛知県・名古屋市・名古屋国際会議場
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 抗炎症性組織再生型M2マクロファージ誘導因子による神経再生療法の開発2015

    • Author(s)
      山本朗仁
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      新潟県・新潟市・新潟コンベンションセンター
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 炎症環境の制御による 組織再生システムの活性化2015

    • Author(s)
      山本朗仁
    • Organizer
      第29回日本医学会総会
    • Place of Presentation
      京都府、京都市、会場名:国立京都国際会議場
    • Year and Date
      2015-04-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 幹細胞の培養液を使った中枢神経再生療法の開発―炎症制御と組織再生の接点2015

    • Author(s)
      山本朗仁
    • Organizer
      第29回日本医学会総会
    • Place of Presentation
      京都府・京都市・国立京都国際会館
    • Year and Date
      2015-04-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Functional recovery after rat spinal cord injury by tissue regenerating factors derived from mesenchymal stem cells2015

    • Author(s)
      山本朗仁
    • Organizer
      第120回日本解剖学会総会・全国学術集会・第92回日本生理学会大会合同大会
    • Place of Presentation
      兵庫県、神戸市、会場名:神戸国際会議場
    • Year and Date
      2015-03-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗炎症環境誘導タンパク複合体によるあらたな再生医療の開発2015

    • Author(s)
      山本朗仁
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      神奈川県、横浜市、会場名:パシフィコ横浜
    • Year and Date
      2015-03-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 幹細胞由来の組織再生因子による次世代再生医療の開発2015

    • Author(s)
      山本朗仁
    • Organizer
      第5回国際放射線神経生物学会大会
    • Place of Presentation
      群馬県、高崎市、会場名:高崎シティギャラリー
    • Year and Date
      2015-02-21
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2019-03-29  

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