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Study of nerve terminal attraction and neuroprotective effect by Schwann cells on diabetic polyneuropathy

Research Project

Project/Area Number 16K09768
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionAichi Medical University

Principal Investigator

Nakamura Jiro  愛知医科大学, 医学部, 教授 (40283444)

Co-Investigator(Kenkyū-buntansha) 加藤 宏一  愛知学院大学, 薬学部, 教授 (40319322)
姫野 龍仁  愛知医科大学, 医学部, 講師 (60753762)
神谷 英紀  愛知医科大学, 医学部, 准教授 (70542679)
Research Collaborator Kondo Masaki  
Miura-Yura Emiri  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords糖尿病性神経障害 / 細胞移植療法 / 幹細胞 / サイトカイン / 血管再生 / 糖尿病性多発神経障害 / シュワン細胞 / 3次元凝集化多能性幹細胞 / 皮膚線維芽細胞 / サイトカイン産生 / NGF / 糖尿病多発神経障害 / 皮膚幹細胞 / Nestin陽性神経前駆細胞 / S100b / GFAP / 神経終末グリア / 糖尿病神経障害 / 皮膚由来神経堤幹細胞 / シュワン前駆細胞
Outline of Final Research Achievements

Improvement of nerve conduction velocity and regeneration of small blood vessels at the transplantation site were confirmed as therapeutic effects in diabetic polyneuropathy (DPN) using skin-derived neural crest stem cell transplantation. It was suggested that differentiation of cytokines secreted from stem cells (PGE2, NGF) and stem cells engrafted at the transplanted site into vascular component cells plays a DPN therapeutic effect.
In secretory factors derived from DPSC (dental pulp stem cells), the neurite outgrowth effect on the peripheral nervous system was confirmed in mouse dorsal root ganglion cells. It was suggested that VEGF is involved in the mechanism of action. Furthermore, in vivo, it was suggested that low molecular weight proteins other than cytokines exert therapeutic effects in DPSC secretion factor.

Academic Significance and Societal Importance of the Research Achievements

今回の成果により糖尿病神経障害の新たな治療法と末梢神経における合併症の発症機転に幹細胞の欠如が関係する可能性が示唆された。今後の糖尿病合併症治療に幹細胞移植療法または、幹細胞から産生されるの液性因子が補充されることで、合併症の進行を止めるだけでなく完治に向けた治療法の確立が可能となることが期待される。社会的な貢献としては、糖尿病合併症の重症化でADLの低下した患者の社会復帰を支援、補完する可能性もある。そのために、できる限り早期の幹細胞移植療法の実現に向けて更なる科学的根拠を積み上げていく所存である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results)

  • [Journal Article] Secreted factors from cultured dental pulp stem cells promoted neurite outgrowth of dorsal root ganglion neurons and ameliorated neural functions in streptozotocin-induced diabetic mice.2019

    • Author(s)
      Miura-Yura E, Tsunekawa S, Naruse K, Nakamura N, Motegi M, Nakai-Shimoda H, Asano S, Kato M, Yamada Y, Izumoto-Akita T, Yamamoto A, Himeno T, Kondo M, Kato Y, Nakamura J, Kamiya H.
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 印刷中

    • NAID

      120006980549

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti‐inflammatory, neuroprotective and angiogenic actions: Cell‐free regenerative medicine for diabetic polyneuropathy2019

    • Author(s)
      Makino Eriko、Nakamura Nobuhisa、Miyabe Megumi、Ito Mizuho、Kanada Saki、Hata Masaki、Saiki Tomokazu、Sango Kazunori、Kamiya Hideki、Nakamura Jiro、Miyazawa Ken、Goto Shigemi、Matsubara Tatsuaki、Naruse Keiko
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 印刷中 Issue: 5 Pages: 1199-1208

    • DOI

      10.1111/jdi.13045

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 末梢神経系の Notchシグナリングおよび神経幹細胞・前駆細胞の マウス糖尿病多発神経障害の 発症機序に及ぼす影響の検討2019

    • Author(s)
      姫野龍仁、John M Hayes、Carey Backus、Jacqueline R Dauch、Claudia Figueroa-Romero、Lucy Hinder、Junguk Hur、Phillipe O’Brien、Eva L Feldman、近藤正樹、恒川新、加藤義郎、神谷英紀、中村二郎
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 皮膚幹細胞球状凝集体由来神経前駆細胞の 糖尿病多発神経障害治療効果と 移植後ミトコンドリア機能回復の検討2017

    • Author(s)
      近藤正樹
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Advances in treatment of diabetic polyneuropathy: For the goal of care and cure2017

    • Author(s)
      近藤正樹、神谷英紀、中村二郎
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Presentation] 皮膚幹細胞球状凝集体由来神経前駆細胞の 糖尿病多発神経障害治療効果と 移植後ミトコンドリア機能回復の検討2017

    • Author(s)
      近藤正樹、姫野龍仁、神谷英紀、中村二郎
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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