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Combination therapy with dental pulp stem cells and histone deacetylase inhibitor against intracerebral hemorrhage in rat

Research Project

Project/Area Number 16K10742
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionNippon Medical School

Principal Investigator

SUDA SATOSHI  日本医科大学, 医学部, 講師 (00366733)

Co-Investigator(Kenkyū-buntansha) 仁藤 智香子  日本医科大学, 医学部, 准教授 (30409172)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords脳出血 / 幹細胞 / ヒストン脱アセチル化酵素阻害剤 / 歯髄幹細胞 / 再生 / 神経保護 / 脳卒中 / 細胞治療 / 歯髄由来幹細胞 / 脳内出血
Outline of Final Research Achievements

One of the characteristics of stroke in Japan is the high incidence of intracerebral hemorrhage (ICH). Dental pulp stem cells (DPSCs) are a potential therapy for ischemic stroke. However, the effect of DPSCs in ICH has not been fully studied. In the present study, we investigated the effects of DPSCs in experimental ICH. ICH was induced by infusion of autologous blood into the left striatum in rats. Twenty-four hours after ICH, rats were randomized to receive an intravenous administration of DPSCs alone, or DPSCs plus valporic acid (VPA), or vehicle. Brain water content, and neurological and immunohistological assessments were performed to examine the effects of these therapies. Combination therapy significantly reduced brain edema in the perihematomal area, and brain atrophy and improved spatial learning and memory and motor functional recovery in rats after ICH.

Academic Significance and Societal Importance of the Research Achievements

本邦の脳卒中の特徴として、脳出血が欧米と比べると発症率が高いことがあります。脳梗塞はカテーテル治療など治療の目覚ましい進歩がありますが、脳出血は機能改善に繋がるような治療はほとんどありません。本研究では、脳出血モデルを用いて、歯髄幹細胞と既存の汎用薬剤であるバルプロ酸の併用療法の効果を認めました。今後、脳出血の治療を前進させる一歩になると考えます。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) (of which Invited: 3 results) Book (1 results)

  • [Journal Article] Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study.2019

    • Author(s)
      Yokobori S, Sasaki K, Kanaya T, Igarashi Y, Nakae R, Onda H, Masuno T, Suda S, Sowa K, Nakajima M, Spurlock MS, Onn Chieng L, Hazel TG, Johe K, Gajavelli S, Fuse A, Bullock MR, Yokota H.
    • Journal Title

      Front Neurol

      Volume: 10 Pages: 1-7

    • DOI

      10.3389/fneur.2019.00082

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transplantation of human dental pulp stem cells ameliorates brain damage following acute cerebral ischemia2018

    • Author(s)
      Nito C, Sowa K, Nakajima M, Sakamoto Y, Suda S, Nishiyama Y, Nakamura-Takahashi A, Nitahara-Kasahara Y, Ueda M, Okada T, Kimura K
    • Journal Title

      Biomed Pharmacother

      Volume: 108 Pages: 1005-1014

    • DOI

      10.1016/j.biopha.2018.09.084

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Dental Pulp Stem Cells Overexpressing Hepatocyte Growth Factor after Cerebral Ischemia/Reperfusion in Rats2018

    • Author(s)
      Sowa K, Nito C, Nakajima M, Suda S, Nishiyama Y, Sakamoto Y, Nitahara-Kasahara Y, Nakamura-Takahashi A, Ueda M, Kimura K, Okada T
    • Journal Title

      Mol Ther Methods Clin Dev

      Volume: 10 Pages: 281-290

    • DOI

      10.1016/j.omtm.2018.07.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 時間で追う脳虚血の病態と治療:(3)慢性期 虚血性脳卒中における歯髄幹細胞をはじめとした細胞治療の展望2019

    • Author(s)
      仁藤智香子
    • Organizer
      日本脳循環代謝学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 脳卒中におけるトランスレーショナル・リサーチ 歯髄由来幹細胞(DPSC)による虚血性脳卒中の治療法開発2019

    • Author(s)
      仁藤智香子
    • Organizer
      神経治療学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 歯髄幹細胞移植による新規脳梗塞治療の開発2019

    • Author(s)
      仁藤智香子
    • Organizer
      第44回日本脳卒中学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ラット局所脳虚血モデルにおけるHGF強発現歯髄幹細胞移植の神経保護効果2017

    • Author(s)
      岨 康太,仁藤智香子, 中島壯崇, 須田 智, 上田雅之, 笠原優子, 今川 究, 平戸徹,岡田尚巳, 木村和美
    • Organizer
      第42回日本脳卒中学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Transplantation of dental pulp stem cells ameliorates brain damage after focal cerebral ischemia2017

    • Author(s)
      仁藤智香子
    • Organizer
      第57回日本神経学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Therapeutic Effect of Human Dental Pulp Stem Cells OverexpressingHepatocyte Growth Factor in Experimental Ischemic Stroke2017

    • Author(s)
      岨康太
    • Organizer
      International Stroke Conference 2018
    • Related Report
      2017 Research-status Report
  • [Book] Cell Therapy against Cerebral Stroke: Comprehensive Reviews for Translational Researches and Clinical Trials.2017

    • Author(s)
      Satoshi Suda
    • Total Pages
      156
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report

URL: 

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

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