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Mechanism of stemness regulation of mesenchymal stem cells on spheroid formation

Research Project

Project/Area Number 19K10192
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57040:Regenerative dentistry and dental engineering-related
Research InstitutionMatsumoto Dental University

Principal Investigator

LI Xianqi  松本歯科大学, 歯学部, 准教授 (60350831)

Co-Investigator(Kenkyū-buntansha) 各務 秀明  松本歯科大学, 総合歯科医学研究所, 教授 (80242866)
溝口 利英  東京歯科大学, 歯学部, 准教授 (90329475)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords間葉系幹細胞 / スフェロイド / stemness / 遺伝子発現 / シグナル / Wntシグナル / 細胞周期 / 体性幹細胞 / 幹細胞マーカー / 接着因子 / インテグリン / 自発的 / 体細胞 / 脱分化
Outline of Research at the Start

本研究では、Tomato遺伝子によって標識した骨髄由来間葉系幹細胞(bone marrow-derived mesenchymal stem cells:BM-MSC)を用い、スフェロイド形成初期から変化する遺伝子、特に細胞接着に関与するインテグリンとその細胞内シグナルを検索する。また、スフェロイドに取り込まれる非幹細胞を蛍光によって同定し、特異的に発現または消失する分子を同定することで、脱分化による幹細胞性獲得のメカニズムの解明を目指す。

Outline of Final Research Achievements

In this study, we used a specific low-adhesion culture plate to form spontaneous spheroids and investigated the gene expression profile after 24 hours. Spontaneous spheroids showed significantly higher expression of stem cell markers, EGF and IGF1, and the expression of GM-CSF were suppressed compared with those of adherent cells. Those results suggest that the signal transduction relating to cell division was accelerated, while the expression of inflammatory cytokines was suppressed during the spontaneous spheroid formation.

Academic Significance and Societal Importance of the Research Achievements

自発的スフェロイドは、高い幹細胞性を有するとともに、生体に近い細胞-細胞間、細胞-細胞外基質間の相互作用を再現することが可能である。スフェロイド形成過程における遺伝子発現の解析は、幹細胞科学の発展のみならず、、安定したスフェロイド培養やスフェロイドに関する評価法の確立など幅広い再生医療の臨床応用や、新たな医薬品開発のためのツールとしての応用も期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (21 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (16 results)

  • [Journal Article] Tissue Engineering with Compact Bone-Derived Cell Spheroids Enables Bone Formation around Transplanted Tooth2022

    • Author(s)
      Matsumura Nahomi、Li Xianqi、Uchikawa-Kitaya Eri、Li Ni、Dong Hongwei、Chen Kai、Yoshizawa Michiko、Kagami Hideaki
    • Journal Title

      Tissue Engineering and Regenerative Medicine

      Volume: 19 Issue: 2 Pages: 377-387

    • DOI

      10.1007/s13770-021-00423-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cryopreserved spontaneous spheroids from compact bone-derived cells as potential ready-to-use products for bone tissue engineering.2021

    • Author(s)
      Dong H, Li X, Chen K, Li N, Kagami H
    • Journal Title

      Tissue Eng Part C Methods.

      Volume: 27 Issue: 4 Pages: 253-263

    • DOI

      10.1089/ten.tec.2021.0001

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of TNF-α and IL-6 on Compact Bone-Derived Cells2021

    • Author(s)
      Zhang Yiming、Li Xianqi、Chihara Takahiro、Dong Hongwei、Kagami Hideaki
    • Journal Title

      Tissue Engineering and Regenerative Medicine

      Volume: 18 Issue: 3 Pages: 441-451

    • DOI

      10.1007/s13770-021-00336-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Alliin inhibits adipocyte differentiation by down-regulating Akt expression: implication for metabolic disease2021

    • Author(s)
      Li N, Chen K, Dong H, Yang J, Yoshizawa M, Kagami H, Li X
    • Journal Title

      Exp Ther Med

      Volume: 21 Issue: 6 Pages: 563-563

    • DOI

      10.3892/etm.2021.9995

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tooth transplantation with a β‐tricalcium phosphate scaffold accelerates bone formation and periodontal tissue regeneration2021

    • Author(s)
      Uchikawa Eri、Yoshizawa Michiko、Li Xianqi、Matsumura Nahomi、Li Ni、Chen Kai、Kagami Hideaki
    • Journal Title

      Oral Diseases

      Volume: 27 Issue: 5 Pages: 1226-1237

    • DOI

      10.1111/odi.13634

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] 皮質骨由来間葉系間質細胞による自発的スフェロイドの特性と骨再生治療への応用2021

    • Author(s)
      李 憲起、董 宏偉、松村奈穂美、芳澤享子、各務秀明
    • Organizer
      第66回(公社)日本口腔外科学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 皮質骨由来細胞スフェロイドは移植歯周囲への骨形成を促進する2021

    • Author(s)
      松村奈穂美、李 憲起、北谷(内川)恵里、董 宏偉、芳澤享子、栗原祐史、各務秀明
    • Organizer
      第64回NPO法人日本口腔科学会中部地方部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 歯冠-歯根発育段階早期歯の移植に関する検討2021

    • Author(s)
      内川恵里、李 憲起、芳澤享子、各務秀明
    • Organizer
      第75回日本口腔科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Effect of cryopreservation on viability, stemness and osteogenic capability of spontaneous spheroids from mouse compact bone derived cells2020

    • Author(s)
      Hongwei Dong, Xianqi Li, Kai Chen, Ni Li, Michiko Yoshizawa, Hideaki Kagami.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Characterization of spontaneous spheroids from oral mucosa-derived cells and their direct comparison with spheroids from skin-derived cells2020

    • Author(s)
      Ni Li, Xianqi Li, Kai Chen, Hongwei Dong, Hideaki Kagami.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウス歯牙移植モデルにおいて骨髄単核球細胞が歯周組織再生に及ぼす効果2020

    • Author(s)
      松村奈穂美、李 憲起、内川恵里、芳澤享子、各務秀明
    • Organizer
      第74回日本口腔科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 骨髄由来単核球を用いた歯の移植に関する基礎的研究2020

    • Author(s)
      内川恵里、李 憲起、松村奈穂美、芳澤享子、各務秀明
    • Organizer
      第74回日本口腔科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] ティッシュエンジニアリングの併用による移植歯周囲への骨形成促進2020

    • Author(s)
      松村 奈穂美,李 憲起,内川恵里,董 宏偉,芳澤享子,各務 秀明
    • Organizer
      第65回(公社)日本口腔外科学会総会・学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Effect of cryopreservation on viability, stemness and osteogenic capability of spontaneous spheroids from mouse compact bone derived cells2020

    • Author(s)
      Hongwei Dong, Xianqi Li, Kai Chen, Ni Li, Michiko Yoshizawa, Hideaki Kagami
    • Organizer
      第19回日本再生医療学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Characterization of spontaneous spheroids from oral mucosa-derived cells and their direct comparison with spheroids from skin-derived cells2020

    • Author(s)
      Ni Li, Xianqi Li, Kai Chen, Hongwei Dong, Hideaki Kagami
    • Organizer
      第19回日本再生医療学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Spontaneously formed spheroids from mouse compact bone-derived cells retain highly potent stem cells with enhanced differentiation capability2019

    • Author(s)
      Kai Chen, Xianqi Li, Ni Li, Hongwei Dong, Michiko Yoshizawa, Hideaki Kagami
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Characterization of spontaneous spheroids from oral mucosa-derived cells and their direct comparison with spheroids from skin-derived cells2019

    • Author(s)
      Ni Li, Xianqi Li, Kai Chen, Hongwei Dong, Michiko Yoshizawa, Hideaki Kagami
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス皮質骨由来幹細胞の生存率および骨形成能に対する凍結保存の影響2019

    • Author(s)
      董 宏偉、李 憲起、陳 凱、李 ニ;、各務秀明
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨再生治療を併用した歯の移植に関する基礎的検討2019

    • Author(s)
      内川恵里,芳澤享子,松村奈穂美, 李憲起,各務秀明
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス歯牙移植モデルにおける骨髄単核球細胞が歯根膜再生に及ぼす効果2019

    • Author(s)
      松村奈穂美、芳澤享子、内川恵里、李 ニ;、陳 凱、董 宏偉、李 憲起、各務秀明
    • Organizer
      第64回日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 皮質骨由来細胞から自発的に形成されたスフェロイドによる骨再生2019

    • Author(s)
      李 憲起、芳澤享子、各務秀明
    • Organizer
      第 23 回日本顎顔面インプラント学会総会・学術大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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