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Development of iPS cell-based tooth regeneration techniques by a transposon-based gene delivery system

Research Project

Project/Area Number 16H05519
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Prosthodontics/ Dental materials science and
Research InstitutionTohoku University

Principal Investigator

Egusa Hiroshi  東北大学, 歯学研究科, 教授 (30379078)

Co-Investigator(Kenkyū-buntansha) 新部 邦透  東北大学, 大学病院, 助教 (50468500)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords再生歯科補綴学 / iPS細胞 / 歯胚再生 / 軟骨再生 / 再生歯学
Outline of Final Research Achievements

The aim of this study was to develop induced pluripotent stem (iPS) cell-based tooth regeneration techniques by a transposon-based tetracycline (tet)-controlled gene regulation system. We focused on BMP-4, an important gene for tooth germ development, and successfully established a tet-controlled BMP-4 gene regulation system for iPS cells in which transcriptional activation of BMP-4 was associated with enhanced mesodermal and non-neuroectodermal lineage commitment. These findings represent an important step toward genetically engineered self-organization of iPS cells, particularly for generation of mesodermal cartilage and non-neuroectodermal organs, such as teeth.

Academic Significance and Societal Importance of the Research Achievements

現在の歯科治療は,失った歯を人工の補綴装置(入れ歯、ブリッジ、インプラント)を用いて補う術式の上に成り立っているが,万能細胞と称されるiPS細胞の発見によって,歯そのものを再生する技術開発に期待が寄せられている。本研究では,細胞内でゲノム上の位置を転移することのできる塩基配列であるトランスポゾンを用いた遺伝子発現制御技術に着目し,歯の発生に重要な遺伝子の発現を操作可能なiPS細胞を作製することで,iPS細胞を軟骨や歯の源基に成り得る細胞に導けることを明らかにした。本研究成果は,試験管内でiPS細胞から歯や軟骨の作製を容易にする可能性を示しており,今後の再生医療への貢献が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 14 results,  Invited: 15 results) Book (1 results)

  • [Journal Article] Current bone substitutes for implant dentistry2018

    • Author(s)
      Yamada M, Egusa H
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 62 Issue: 2 Pages: 152-161

    • DOI

      10.1016/j.jpor.2017.08.010

    • NAID

      130006733089

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Challenges for stem cell-based “regenerative prosthodontics”2017

    • Author(s)
      Niibe K, Suehiro F, Oshima M, Nishimura M, Kuboki T, Egusa H
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 61 Issue: 1 Pages: 3-5

    • DOI

      10.1016/j.jpor.2016.09.001

    • NAID

      130005465202

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The potential of enriched mesenchymal stem cells with neural crest cell phenotypes as a cell source for regenerative dentistry2017

    • Author(s)
      Niibe K, Zhang M, Nakazawa K, Morikawa S, Nakagawa T, Matsuzaki Y, Egusa H
    • Journal Title

      Jpn Dent Sci Rev

      Volume: 印刷中 Issue: 2 Pages: 25-33

    • DOI

      10.1016/j.jdsr.2016.09.001

    • NAID

      50012041277

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] iPS細胞が描く歯科医療の未来2019

    • Author(s)
      江草 宏
    • Organizer
      群馬県歯科医学会学術大会 特別講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Establishment of a method for fabricating osteochondral constructs from induced pluripotent stem cells2019

    • Author(s)
      Limraksasin P, Egusa H.
    • Organizer
      第8回補綴若手研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] In vitro bone tissue fabrication by using iPS cells2018

    • Author(s)
      Hiroshi Egusa
    • Organizer
      The 96th IADR General Session, 国際シンポジウム“Biodental Engineering-Towards Real Tissue Synthesis in vitro”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of a novel technology for targeted differentiation of iPS cells by Notch signaling inducible biomaterials2018

    • Author(s)
      Hiroshi Egusa
    • Organizer
      日本学術振興会/タイ学術会議合同国際シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS cell-based strategies in bone tissue engineering2018

    • Author(s)
      Hiroshi Egusa
    • Organizer
      5th Airlangga University Joint Scientific Meeting in Dentistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS cell-based strategies for bone and cartilage bioengineering2018

    • Author(s)
      Hiroshi Egusa
    • Organizer
      2018 Chonnam National University School of Dentistry & Dental Hospital International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS Cell-Based Strategies for Bone Tissue Engineering2018

    • Author(s)
      Hiroshi Egusa
    • Organizer
      China-Japan Dental Science Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS Cell-Based Strategies for Bone Bioengineering2018

    • Author(s)
      Hiroshi Egusa
    • Organizer
      Chulalongkorn University Symposium 国際シンポジウム “Trends in Regenerative Dentistry”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Controlled transcriptional regulation of transgene expression during osteogenic differentiation of mouse induced pluripotent stem cells2018

    • Author(s)
      Kondo T, Zhang M, Kamano Y, Okawa H, Egusa H.
    • Organizer
      International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro bone fabrication by controlled BMP2 expression in iPSCs2018

    • Author(s)
      Kondo T, Zhang M, Kamano Y, Okawa H, Egusa H.
    • Organizer
      96th IADR General Session
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone tissue engineering approach by genetic modification of induced pluripotent stem cells2018

    • Author(s)
      Kondo T, Zhang M, Egusa H.
    • Organizer
      13th International Workshop on Biomaterials in Interface Science
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A stepwise protocol for efficient osteogenic induction of human induced pluripotent stem cells2018

    • Author(s)
      Kondo T, Okawa H, Horie N, Egusa H.
    • Organizer
      5th Airlangga University Joint Scientific Meeting in Dentistry(JSMiD)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fabrication of lyophilized bioengineered bone grafts using genetically modified iPSCs2018

    • Author(s)
      Kondo T, Okawa H, Egusa H
    • Organizer
      66th Annnual Meeting of JADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS cell-based strategies in bone tissue engineering2017

    • Author(s)
      Egusa H
    • Organizer
      The 2nd Annual Academic Conference of Society of Dental Research Administration, CSA
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS細胞を用いた骨再生医療戦略2017

    • Author(s)
      江草 宏
    • Organizer
      東北大学金属材料研究所共同研究ワークショップ
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Emerging approaches for “regenerative prosthodontics”2017

    • Author(s)
      Egusa H
    • Organizer
      2017 Biennial Joint Congress of JPS-CPS-KAP
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS cell-based strategies in bone tissue engineering2017

    • Author(s)
      Egusa H
    • Organizer
      第65回 国際歯科研究学会 日本部会(JADR)学術大会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] インプラント臨床における再生医療の現状と挑戦2017

    • Author(s)
      江草 宏
    • Organizer
      第37回日本口腔インプラント学会 近畿・北陸支部学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 再生歯科医療を材料と生体から理解する2016

    • Author(s)
      江草 宏
    • Organizer
      大阪口腔インプラント研究会例会 シンポジウム「組織再生の最前線」
    • Place of Presentation
      大阪市
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] iPS細胞が描く歯科医療の未来 ~これからの再生歯科医療への期待と課題~2016

    • Author(s)
      江草 宏
    • Organizer
      第69回東北地区歯科医学会
    • Place of Presentation
      仙台市
    • Year and Date
      2016-11-05
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた骨組織再生技術の開発2016

    • Author(s)
      江草 宏
    • Organizer
      第59回春季日本歯周病学会学術大会 シンポジウム「大規模歯周組織再生を目指した細胞治療開発の新展開」
    • Place of Presentation
      鹿児島市
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] Gene delivery and expression systems in induced pluripotent stem cells: In "Interface Oral Health Science 2016"2017

    • Author(s)
      Zhang M, Niibe K, Kondo T, Kamano Y, Saeki M, Egusa H.
    • Total Pages
      13
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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