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Elucidation of signaling mechanisms through leptin receptors in bone marrow mesenchymal stem cells

Research Project

Project/Area Number 18K17034
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionKeio University

Principal Investigator

Ouchi Takehito  慶應義塾大学, 医学部(信濃町), 助教 (30803564)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords間葉系幹細胞 / 造血幹細胞 / LepR / JAK2/STAT3 / JAK2/STAT3経路 / db/dbマウス / Leptin受容体
Outline of Final Research Achievements

Blood cells and vascular endothelial cells were analyzed with a flow cytometer using wild-type mice and db/db mice, and then LepR(+) cells were isolated. After LepR(+) cells isolation, the cells were cultured in vitro and the properties of mesenchymal stem cells were analyzed. When the self-renewal ability and other functional analyzes were evaluated by maintenance culture by the adhesive culture method, there was no difference in colony forming ability, doubling time, and migration ability. There was no significant difference in the ability to differentiate into bone and cartilage between wild-type mice and db/db mice, but db/db mice showed high differentiation potential in terms of fat differentiation. No difference in hematopoietic function was observed between wild-type and db/db mice, suggesting that JAK2/STAT3 impairment and adipose differentiation characteristics may not affect hematopoiesis.

Academic Significance and Societal Importance of the Research Achievements

骨髄移植は口腔粘膜疾患を伴うなど、口腔領域と密接に関連する。骨髄移植は造血幹細胞移植と定義されることが多いが、実際には造血幹細胞に加えてもう一つの幹細胞である間葉系幹細胞を含む。そのため、骨髄移植の成果に間葉系幹細胞が関わっている可能性が十分考えられる。近年、間葉系幹細胞の有効なマーカーとして報告されたLepRに着目し、本研究ではLepRシグナル経路と骨髄幹細胞の関係性に着目した。生体内・外でLepRシグナル経路が骨髄環境にどのように影響をもたらしているかを明らかにすることで、そのシグナル機構の調節により骨髄疾患に対する新たな治療法の開発や予防法の開発へとつながる可能性が示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] Harvard School of Dental Medicine/Harvard Stem Cell Institute(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Mesenchymal stem cell-based tissue regeneration therapies for periodontitis2020

    • Author(s)
      Ouchi T, Nakagawa T
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 72-78

    • DOI

      10.1016/j.reth.2019.12.011

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting the Tumor Stroma for Oral Cancer Therapy2019

    • Author(s)
      Ouchi T, Morikawa S, Asoda S
    • Journal Title

      Modern Research in Dentistry

      Volume: 4 Issue: 3

    • DOI

      10.31031/mrd.2019.04.000586

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] iPS cell technology for periodontal tissue regeneration2019

    • Author(s)
      Takehito Ouchi, Taneaki Nakagawa
    • Journal Title

      Impact

      Volume: 2 Issue: 2 Pages: 30-32

    • DOI

      10.21820/23987073.2019.2.30

    • Related Report
      2018 Research-status Report
    • Open Access
  • [Journal Article] Experimental Study On Vertical Variations Of Unilateral Extension Base Flexible Removable Dentures2019

    • Author(s)
      Nobuyuki Horie, Takehito Ouchi, Rumiko Nishiyama, Sho Usuda, Satoru Morikawa, Seiji Asoda, Taneaki Nakagawa
    • Journal Title

      The Bulletin of Tokyo Dental College

      Volume: -

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 紡錘細胞癌における間葉系幹細胞の同定とPDGFRα阻害薬を用いた細胞死の誘導2020

    • Author(s)
      黄地健仁,森川暁,高橋萌,吉川桃子,相馬智也,宮下英高,河奈裕正,中川種昭,莇生田整治
    • Organizer
      第74回NPO法人日本口腔科学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Stem cells identified in the crescent region in adult periodontal microenvironment are regulated by Hedgehog signaling2020

    • Author(s)
      Takehito Ouchi, Bo Li, Yingzi Yang
    • Organizer
      Keystone Symposia eSymposia meeting eSymposia | Tissue Plasticity: Preservation and Alteration of Cellular Identity
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CXCL12-Hedgehog signaling regulates calvaria homeostasis and injury repair2020

    • Author(s)
      Bo Li, Takehito Ouchi, Yingzi Yang
    • Organizer
      Keystone Symposia eSymposia meeting eSymposia | Tissue Plasticity: Preservation and Alteration of Cellular Identity
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stem cells identified in the periodontal crescent region are regulated by CXCL12 and Hedgehog signaling2020

    • Author(s)
      Takehito Ouchi
    • Organizer
      Bone Research Workshop
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞由来LNGFR/THY-1強陽性神経堤様細胞は間葉系幹細胞の性質をもつ2018

    • Author(s)
      黄地健仁,岡野栄之,森川暁,中川種昭
    • Organizer
      第61回春季日本歯周病学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] ゾレドロン酸およびデノスマブ関連顎骨壊死と有床義歯との関連性に関する臨床的検討2018

    • Author(s)
      浅野崇浩,黄地健仁,工藤葉子,岡村衣里子,臼田頌,海住直樹,新部邦透,岩﨑良太郎,有馬誠亮,西山留美子,鈴木啓介,鈴木潔,中川種昭,堀江伸行
    • Organizer
      公益社団法人日本補綴歯科学会第127回学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 神経堤由来間質細胞から骨分化に関わるマーカーの探索2018

    • Author(s)
      黄地健仁,柳沢託磨,根岸智史,岡野栄之,中川種昭
    • Organizer
      第61回秋季日本歯周病学会学術大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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