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Reconstruction of three-dimensional Alzheimer's disease model in vitro and development of novel treatment by human dental pulp stem cells

Research Project

Project/Area Number 17K11813
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dental engineering/Regenerative dentistry
Research InstitutionThe Nippon Dental University

Principal Investigator

Xiao Li  日本歯科大学, 生命歯学部, 講師 (80548256)

Co-Investigator(Kenkyū-buntansha) 佐伯 周子  日本歯科大学, 生命歯学部, 准教授 (90281435)
岡村 尚  日本歯科大学, 生命歯学部, 助教 (80795154)
Project Period (FY) 2017-04-01 – 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 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords神経再生 / アルツハイマー病 / ヒト歯髄幹細胞 / 酸化ストレス / アミロイドβ / 酸化ストレス耐性 / ヒト乳歯歯髄細胞 / 神経保護 / 培養脳スライス / 神経細胞新生 / 海馬組織 / ヒト歯髄由来幹細胞 / 中枢神経再生 / 再生医学 / 細胞組織 / 神経科学 / 老化
Outline of Final Research Achievements

This study first reconstructed an in vitro three-dimensional model of Alzheimer's disease. Oxidative stress-tolerant stem cells from human exfoliated deciduous teeth (OST-SHED) were created by H2O2-stimulation. OST-SHED could protect the brain tissue from oxidative stress, reduce the accumulation of amyloid β (Aβ), and increase activity of Neprilysin (one of the Aβdegrading enzymes). Although OST-SHED had lower cell viability, the neuronal protection
of OST-SHED was significantly superior to that of normal SHED. Our findings suggest that SHED, especially OST-SHED, could prevent oxidative stress induced brain damage and improve the pathology of Alzheimer's disease. OST-SHED can be explored as a new therapeutic tool for IBD, TBI and neurodegenerative disorders.

Academic Significance and Societal Importance of the Research Achievements

本研究は初めてIn vitroにおいてアルツハイマー病の病態モデルを構築し、酸化ストレス耐性歯髄幹細胞の開発に成功した。この病態モデルと酸化ストレス耐性歯髄幹細胞を用いて、神経再生、抗酸化、Aβクリアランス促進、抗老化を総合的に行う治療法を開発し、世界に先駆けて認知症を始めとする神経変性疾患の根本的な治療法を開発することにつながると考えられる。

Report

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

    (14 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results) Presentation (2 results)

  • [Int'l Joint Research] Dong-E-E-Jiao Co. Ltd(中国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ACE2: The key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel?2020

    • Author(s)
      Xiao Li、Sakagami Hiroshi、Miwa Nobuhiko
    • Journal Title

      Viruses

      Volume: 12 Issue: 5 Pages: 491-491

    • DOI

      10.3390/v12050491

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enzyme-digested Colla Corii Asini (E’jiao) prevents hydrogen peroxide-induced cell death and accelerates amyloid beta clearance in neuronal-like PC12 cells.2020

    • Author(s)
      Xiao L, Liao F, Ide R,et al.
    • Journal Title

      Neural Regen Res.

      Volume: In press Pages: 00-00

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 新型コロナウイルス感染症に対する最新知見と有効な漢方薬2020

    • Author(s)
      肖 黎
    • Journal Title

      New Food Industry

      Volume: 62 Pages: 181-184

    • NAID

      40022176880

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 手作りマスク安全なの?マスク用生地のフィルター性能簡易測定法の開発2020

    • Author(s)
      肖 黎
    • Journal Title

      New Food Industry

      Volume: 62 Pages: 412-414

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] コロナストレスと楽しい研究生活2020

    • Author(s)
      肖 黎
    • Journal Title

      New Food Industry

      Volume: 62 Pages: 443-444

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new method for testing filtration efficiency of mask materials under sneeze-like pressure2020

    • Author(s)
      Xiao Li、Sakagami Hiroshi、Miwa Nobuhiko
    • Journal Title

      In vivo

      Volume: In press Pages: 00-00

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 漢方の効能(7)インフルエンザ,漢方薬と腸内細菌叢2019

    • Author(s)
      肖 黎
    • Journal Title

      New Food Industry

      Volume: 61 Pages: 397-398

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative Stress-Tolerant Stem Cells from Human Exfoliated Deciduous Teeth Decrease Hydrogen Peroxide-Induced Damage in Organotypic Brain Slice Cultures from Adult Mice2019

    • Author(s)
      Xiao Li、Saiki Chikako、Okamura Hisashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 8 Pages: 1858-1858

    • DOI

      10.3390/ijms20081858

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biological effects of traditional Chinese medicine Corii colla asini,2019

    • Author(s)
      Xiao L, Liao F, Zhou XS
    • Journal Title

      New Food Indust

      Volume: 61 Pages: 65-72

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Three-dimensional Inflammatory Human Tissue Equivalents of Gingiva2018

    • Author(s)
      Xiao Li、Okamura Hisashi、Kumazawa Yasuo
    • Journal Title

      Journal of Visualized Experiments

      Volume: 134 Issue: 134

    • DOI

      10.3791/57157

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human Dental Pulp Cells Differentiate toward Neuronal Cells and Promote Neuroregeneration in Adult Organotypic Hippocampal Slices In Vitro2017

    • Author(s)
      Xiao Li、Ide Ryoji、Saiki Chikako、Kumazawa Yasuo、Okamura Hisashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 8 Pages: 1745-1745

    • DOI

      10.3390/ijms18081745

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト歯性幹細胞は成体マウス脳スライスにおける神経新生促進作用及び酸化ストレスによる細胞死に対する防御作用2019

    • Author(s)
      肖黎、佐伯周子、井出良治
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 成体マウス海馬スライスの神経細胞の新生に対するヒト歯髄由来幹細胞の促進作用2018

    • Author(s)
      肖 黎,井出良治,佐伯周子,熊澤康雄,岡村 尚
    • Organizer
      第36回日本ヒト細胞学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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