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Identification and expansion of sensory epithelial stem cell from human inner ear organoid

Research Project

Project/Area Number 21K09638
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Nakamura Takashi  京都府立医科大学, 医学(系)研究科(研究院), 助教 (80724179)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords内耳オルガノイド / 内耳有毛細胞 / SOX2 / 内耳再生医療 / 内耳オルガノイド培養 / 感覚上皮幹細胞 / 内耳再生
Outline of Research at the Start

再生医療には分化誘導療法と細胞移植療法の二種類が存在する。眼科や整形外科の分野では、すでに後者による再生医療が臨床応用されいている。一方で、内耳の細胞移植療法に関しては、動物実験による研究成果は蓄積されつつあるものの、ヒトに有効な治療法は未だ存在しない。これは、ヒト由来の内耳幹細胞培養技術が存在しないことが主な要因ではないかと考えられる。そこでヒトES細胞を分化させた内耳オルガノイドから、内耳幹細胞を同定し、単離培養する実験を考案した。これを再度培養・増殖させることにより、将来的にはこれを細胞移植療法に適用することで、ヒト内耳再生を実現できる可能性を秘めている。

Outline of Final Research Achievements

In this study, we attempted to isolate and culture LGR5 and SOX2 positive inner ear stem cells from inner ear organoids differentiated from human ES cells. While isolation and culture of the former proved challenging due to low expression efficiency, the latter was successfully isolated and cultured using reporter cells. This enabled us to analyze the characteristics of sensory epithelial cells and confirm their potential to differentiate into inner ear hair cells. Notably, organoid induction experiments using SOX2 positive cells demonstrated higher efficiency in the expression of genes specific to inner ear hair cells compared to traditional methods.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、内耳再生医療の実現に向けた重要な一歩となる可能性を秘めている。難聴患者数が増加する中、内耳有毛細胞の再生を目指した本技術は、感音難聴の根本的な治療法開発に貢献すると考えられる。また、内耳オルガノイドを用いた新たな研究手法は、内耳の発生や病態解明にも寄与し、再生医療分野全体の進展に寄与することが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Generating high-fidelity cochlear organoids from human pluripotent stem cells2023

    • Author(s)
      Moore Stephen T.、Nakamura Takashi、Nie Jing、Solivais Alexander J.、Aristiz?bal-Ram?rez Isabel、Ueda Yoshitomo、Manikandan Mayakannan、Reddy V. Shweta、Romano Daniel R.、Hoffman John R.、Perrin Benjamin J.、Nelson Rick F.、Frolenkov Gregory I.、Chuva de Sousa Lopes Susana M.、Hashino Eri
    • Journal Title

      Cell Stem Cell

      Volume: 30 Issue: 7 Pages: 950-961.e7

    • DOI

      10.1016/j.stem.2023.06.006

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Defining developmental trajectories of prosensory cells in human inner ear organoids at single-cell resolution2023

    • Author(s)
      Ueda Yoshitomo、Nakamura Takashi、Nie Jing、Solivais Alexander J.、Hoffman John R.、Daye Becca J.、Hashino Eri
    • Journal Title

      Development

      Volume: 150 Issue: 12

    • DOI

      10.1242/dev.201071

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 聴覚・平衡覚機能再生に向けた幹細胞トランスレーショナルリサーチ ヒトオルガノイドモデルを用いた内耳研究の展望2022

    • Author(s)
      中村 高志
    • Organizer
      第32回日本耳科総会・学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] Generation and application of human inner ear organoid containing vestibular and cochlear like hair cells.2022

    • Author(s)
      Takashi Nakamura
    • Organizer
      4th World Congress on Endoscopic Ear Surgery
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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