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Establishment of minimally invasive cleft palate closure treatment using mesenchymal stem cell-derived exosome from human exfoliated deciduous teeth

Research Project

Project/Area Number 19K19269
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionHiroshima University

Principal Investigator

Abe Takaharu  広島大学, 病院(歯), 助教 (20806682)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsMSC / SHED / 骨再生 / SHED-CM / エクソソーム / CD146 / Microarray / CD31 / CD34 / bone regeneration / 日本矯正歯科学会 / Oral Disease / 再生歯学 / 間葉系幹細胞
Outline of Research at the Start

本研究は、SHED-CMよりエクソソームを抽出し、SHEDエクソソームのシグナル伝達機構を探索する。また、SHEDのエクソソームを応用することで、組織骨再生について評価する。
初年度では、in vitro系の実験を行う。ヒト乳歯の歯髄組織より、歯髄由来間葉系幹細胞およびそれらの培養上清よりエクソソームを精製し、その性質について比較・検討を行う。
次年度では、免疫不全マウスを用い、頭蓋骨に欠損部を作製し、SHEDエクソソームを投与することにより骨再生の程度についてCTによる三次元解析および組織学的に検証する。

Outline of Final Research Achievements

In order to reduce the invasion of cleft lip and/or palate palate patients' secondary grafting, a study of bone regeneration therapy using deciduous pulp-derived mesenchymal stem cells (SHED) was conducted. In the first year, it was clarified that good bone regeneration can be achieved by transplanting carrier (atelocollagen) and SHED conditioned media (SHED-CM)into a bone defect prepared in a mouse skull.
In the next year, in order to improve the transplantation efficiency, CD146-positive, which is known as a cell adhesion molecule, was isolated from SHED and applied to transplantation. As a result, it was clarified that significantly good bone regeneration was produced. Furthermore, analysis of exosomes in SHED-CM is progressing, focusing on microRNAs contained in the factors.

Academic Significance and Societal Importance of the Research Achievements

近年乳歯歯髄由来間葉系幹細胞は着目されているものの、その詳細な性質については不明な点が多い。本研究では、SHED中に含有される液性成分について解析し、また、その成分を移植に応用することで、良好な骨再生を生じることを明らかとした。
本研究で用いたSHEDを応用し更なる骨再生機構の解明を試みることで、歯科医学にとどまらず広く再生医療分野の進歩へ貢献を果たすと考えられる。さらに、本法を臨床応用し患者の負担が軽減し、低侵襲で良好な骨再生療法を確立することは、社会的観点から重要な意義がある。

Report

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

    (6 results)

All 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Stem cell-derived conditioned media from human exfoliated deciduous teeth promote bone regeneration.2020

    • Author(s)
      Hiraki T, Kunimatsu R, Nakajima K, Abe T, Yamada S, Rikitake K, Tanimoto K
    • Journal Title

      Oral diseases

      Volume: 26 Issue: 2 Pages: 381-390

    • DOI

      10.1111/odi.13244

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Examination of the effect of combined use of Nd: YAG laser irradiation and mechanical force loading on bone metabolism using cultured human osteoblasts2020

    • Author(s)
      Tsuka Y., Kunimatsu R., Gunji H., Abe T., Concepcion M C., Nakajima K., Kimura A., Hiraki T., Nakatani A., Tanimoto K
    • Journal Title

      J Laser Med Sci

      Volume: 11 Issue: 2 Pages: 138-143

    • DOI

      10.34172/jlms.2020.24

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Baicalin inhibits root resorption during tooth movement in a rodent mode2020

    • Author(s)
      Kunimatsu R., Kimura A., Tsuka Y., Horie K., Yoshimi Y., Awada T., Gunji H., Abe T., Nakajima K., Sakata S., Nakatani A., Tanimoto K
    • Journal Title

      Archives of Oral Biology

      Volume: 116 Pages: 1-8

    • DOI

      10.1016/j.archoralbio.2020.104770

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Examination of the effect of combined use of Er:YAG laser irradiation and mechanical force loading on bone metabolism using primary human gingival fibroblasts2020

    • Author(s)
      Tsuka Y, Kunimatsu R, Gunji H, Abe T, Medina CC, Hiraki T, Nakatani A, Sakata S, Rikitake K, Aisyah PN, Hirose N, Yanosita M, Tanimoto K.
    • Journal Title

      Lasers Med Sci

      Volume: 35(9) Issue: 9 Pages: 2059-2064

    • DOI

      10.1007/s10103-020-03079-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 乳歯歯髄由来間葉系幹細胞の培養上清の骨再生治療への応用2019

    • Author(s)
      平木智香、國松亮、中島健吾、阿部崇晴、山田桜、力武航大、粟田哲也、吉見友希、柄優至、加来真人、谷本幸太郎
    • Organizer
      日本矯正歯科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 未分化間葉系幹細胞が破骨細胞前駆細胞の走化作用へ及ぼす影響2019

    • Author(s)
      阿部崇晴、國松亮、吉見友希、柄優至、粟田哲也、中島健吾、平木智香、力武航大、鷲見圭輔、 谷本幸太郎
    • Organizer
      日本矯正歯科学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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