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Development of cell transplantation therapy using pluripotent stem cells for severe vestibular disorders

Research Project

Project/Area Number 18K16903
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionNara Medical University

Principal Investigator

Sakagami Masaharu  奈良県立医科大学, 医学部附属病院, 研究員 (50745437)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords内耳有毛細胞 / ES細胞 / 内耳再生 / 分化誘導 / 前庭 / 高度前庭障害 / マウス
Outline of Final Research Achievements

Vestibular hair cells (V-HCs) in the inner ear have important roles and various functions. When V-HCs are damaged, crippling symptoms, such as vertigo, visual field oscillation, and imbalance, are often seen. Recently, several studies have reported differentiation of embryonic stem (ES) cells, as pluripotent stem cells, to HCs, though a method for producing V-HCs has yet to be established. In the present study, we used vestibular cell conditioned medium (V-CM) and effectively induced ES cells to differentiate into V-HCs. Expressions of V-HCrelated markers (Math1, Myosin6, Brn3c, Dnah5) were significantly increased in ES cells cultured in V-CM for 2weeks, while those were not observed in ES cells cultured without V-CM. On the other hand, the cochlear HCrelated marker Lmod3 was either not detected or detected only faintly in those cells when cultured in V-CM. This results demonstrate that V-CM has an ability to specifically induce differentiation of ES cells into V-HCs.

Academic Significance and Societal Importance of the Research Achievements

本研究により、前庭細胞由来液性因子を用いることで、前庭有毛細胞への特異的分化誘導制御が実現可能となった。この新しい知見は、内耳再生医学の基礎的視点から前庭有毛細胞の分化・再生メカニズムを解明する上で重要と考えられる。

Report

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

    (4 results)

All 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Differentiation of embryonic stem cells into inner ear vestibular hair cells using vestibular cell derived-conditioned medium2019

    • Author(s)
      Sakagami M, Ouji Y, Kawai N, Misu M, Yoshikawa M, Kitahara T.
    • Journal Title

      Biochem Biophys Rep

      Volume: 19 Pages: 100649-100649

    • DOI

      10.1016/j.bbrep.2019.100649

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 卵形嚢由来細胞を用いたES細胞から内耳前庭有毛細胞への分化誘導法の開発2019

    • Author(s)
      阪上雅治、王寺幸輝、北原糺、吉川正英
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Differentiation of mouse embryonic stem cells into inner ear cell-like cells using vestibular cell-conditioned medium2018

    • Author(s)
      Sakagami M, Ouji Y, Kawai N, Kitahara T, Yoshikawa M
    • Organizer
      16th International Society for Stem Cell Research Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ES細胞から内耳前庭有毛細胞への効率的分化誘導法の開発2018

    • Author(s)
      阪上雅治、王寺幸輝、北原糺、吉川正英
    • Organizer
      第28回日本耳科学会 総会・学術講演会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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