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In vitro modeling of human bone metabolism using pluripotent stem cell-derived bone organoids

Research Project

Project/Area Number 18K19635
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionNagasaki University (2019-2020)
The University of Tokyo (2018)

Principal Investigator

OHBA Shinsuke  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (20466733)

Co-Investigator(Kenkyū-buntansha) 疋田 温彦  東京大学, 医学部附属病院, 特任研究員 (60443397)
北條 宏徳  東京大学, 大学院医学系研究科(医学部), 准教授 (80788422)
Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords骨代謝
Outline of Final Research Achievements

We aimed to develop in vitro culture systems that recapitulated the three-dimensional bone microenvironment using pluripotent stem cells (PSCs) and live imaging methods that enabled to visualize cellular dynamics underlying coupling of bone resorption and formation in the culture systems. We have established a protocol for directing PSCs toward osteoblasts and osteocytes, and developed methods to generate bone-like tissues by culturing the PSC-derived cells in a three-dimensional manner. We have also developed a platform for observation and quantification of cellular interaction in the three-dimensional culture using two-photon microscopes.

Academic Significance and Societal Importance of the Research Achievements

生体骨組織の骨リモデリングにおける個々の細胞機能の改善や調節ではなく、複数の細胞種からなる骨微小環境そのものを標的とした骨代謝回転の改善は、骨粗鬆症治療に資するものと考えられる。そのためには特にヒトにおけるカップリング機構の正しい理解が必須であり、その解析を可能とする研究システムの開発が急務である。したがって、本研究で得られた成果は、ヒト多能性幹細胞を用いて、骨微小環境を三次元的に再現するヒト骨オルガノイドを作製し、ライブイメージング技術によって、カップリングにおける細胞動態の可視化・観察を可能にするシステムの開発につながることが期待される。

Report

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

    (23 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Connecticut Health Center/Stanford University(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Connecticut Health Center/Stanford University(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Connecticut Health Center(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] The Progress of Stem Cell Technology for Skeletal Regeneration2021

    • Author(s)
      Tani Shoichiro、Okada Hiroyuki、Chung Ung-il、Ohba Shinsuke、Hojo Hironori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1404-1404

    • DOI

      10.3390/ijms22031404

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold2020

    • Author(s)
      Uto Sakura、Hikita Atsuhiko、Sakamoto Tomoaki、Mori Daisuke、Yano Fumiko、Ohba Shinsuke、Saito Taku、Takato Tsuyoshi、Hoshi Kazuto
    • Journal Title

      Tissue Engineering Part A

      Volume: - Issue: 9-10 Pages: 604-617

    • DOI

      10.1089/ten.tea.2020.0106

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stepwise strategy for generating osteoblasts from human pluripotent stem cells under fully defined xeno-free conditions with small-molecule inducers2020

    • Author(s)
      Zujur Denise、Kanke Kosuke、Onodera Shoko、Tani Shoichiro、Lai Jenny、Azuma Toshifumi、Xin Xiaonan、Lichtler Alexander C.、Rowe David W.、Saito Taku、Tanaka Sakae、Masaki Hideki、Nakauchi Hiromitsu、Chung Ung-il、Hojo Hironori、Ohba Shinsuke
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 19-31

    • DOI

      10.1016/j.reth.2019.12.010

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An osteogenic helioxanthin derivative suppresses the formation of bone-resorbing osteoclasts.2019

    • Author(s)
      Amano H, Iwaki F, Oki M, Aoki K, Ohba S
    • Journal Title

      Regen Ther

      Volume: 11 Pages: 290-296

    • DOI

      10.1016/j.reth.2019.08.007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Switching of cell proliferation/differentiation in thiol-maleimide clickable microcapsules triggered by in situ conjugation of biomimetic peptides.2019

    • Author(s)
      Oki Y, Kirita K, Ohta S, Ohba S, Horiguchi I, Sakai Y, Ito T
    • Journal Title

      Biomacromolecules

      Volume: 20 Issue: 6 Pages: 2350-2359

    • DOI

      10.1021/acs.biomac.9b00333

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation2019

    • Author(s)
      Yano Fumiko、Ohba Shinsuke、Murahashi Yasutaka、Tanaka Sakae、Saito Taku、Chung Ung-il
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 7666-7666

    • DOI

      10.1038/s41598-019-43948-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment of Bone Defects by Transplantation of Genetically Modified Mesenchymal Stem Cell Spheroids2018

    • Author(s)
      Yanagihara K, Uchida S, Ohba S, Kataoka K, Itaka K
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 9 Pages: 358-366

    • DOI

      10.1016/j.omtm.2018.04.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨軟骨形成機構の理解に向けて2020

    • Author(s)
      大庭伸介
    • Organizer
      第62回日本顕微鏡学会九州支部集会・学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Generation of skeletal cells from pluripotent stem cells.2020

    • Author(s)
      Shinsuke Ohba
    • Organizer
      The 68th Meeting of Japanese Association for Dental Research
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Runx2 defines the osteoblast chromatin landscape in skeletal development.2020

    • Author(s)
      Hojo H, Saito T, Onodera S, Azuma T, Chung UI, Seki M, Suzuki Y, McMahon AP, Ohba S
    • Organizer
      42nd Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨・軟骨の形成における遺伝子発現制御機構の探索.2020

    • Author(s)
      大庭伸介
    • Organizer
      第125回日本解剖学会総会・全国学術集会(誌上開催)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 多能性幹細胞由来の骨形成性細胞の作製と応用.2019

    • Author(s)
      大庭伸介
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 骨・軟骨発生の理解と多能性幹細胞を用いた発生過程の再現.2019

    • Author(s)
      大庭伸介
    • Organizer
      日本解剖学会第75回九州支部学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Generation of functional salivary gland organoid from mouse embryonic stem cells by Sox9 and Foxc1 transduction.2019

    • Author(s)
      Tanaka J, Ogawa M, Hojo H, Mabuchi Y, Yasuhara R, Takamatsu K, Ohba S, Tsuji T, Mishima K
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of bone marrow mesenchymal stromal cell population and stem cell niche signal.2019

    • Author(s)
      Kanazawa S, Hojo H, Ohba S, Hikita A, Hamada Y, Hoshi K
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞の分化システムとChIP-seqを駆使して骨芽細胞分化における転写制御を理解する2018

    • Author(s)
      大庭伸介
    • Organizer
      第60回歯科基礎医学会学術大会・総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた骨芽細胞分化のインビトロモデリングと分化機序解析への応用2018

    • Author(s)
      大庭伸介
    • Organizer
      第4回日本筋学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 骨再生療法・基礎的観点から2018

    • Author(s)
      大庭伸介
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] 長崎大学大学院医歯薬学総合研究科細胞生物学分野

    • URL

      http://www.de.nagasaki-u.ac.jp/dokuji/kaibou-2/

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Patent(Industrial Property Rights)] 椎板細胞の製造方法および該椎板細胞の利用2021

    • Inventor(s)
      大庭伸介、谷彰一郎、北條宏徳、鄭雄一
    • Industrial Property Rights Holder
      国立大学法人長崎大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-041384
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-07-25   Modified: 2022-01-27  

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