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Elucidation of pathogenic mechanisms of sensorineural hearing loss and establishment of disease model using XP-A patient-derived iPS cells

Research Project

Project/Area Number 15K10748
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionKyoto University

Principal Investigator

Hireo Ohnishi  京都大学, 医学研究科, 研究員 (50397634)

Co-Investigator(Kenkyū-buntansha) 北尻 真一郎  信州大学, 学術研究院医学系(医学部附属病院), 講師 (00532970)
中川 隆之  京都大学, 医学研究科, 講師 (50335270)
Research Collaborator YUBA shyunsuke  
MATSUDA toshirou  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords疾患特異的iPS細胞 / 神経分化誘導 / 聴神経 / 内耳感覚上皮組織培養 / 色素性乾皮症 / 神経細胞 / シナプス形成 / 共培養 / 分化誘導
Outline of Final Research Achievements

To generate auditory nerve degeneration model for XP-A patients, we induced glutamatergic neurons from patient-derived iPSCs using our established induction method. And we generated in vitro model using normal hiPSCs for examination of neuronal functions. We observed the neurite outgrowth into cochlea explants in co-culture. Moreover, to examine the neuronal functions of hiPSC-derived neuron, hiPSC-derived neural stem cells were cultured with vestibular explants and then we performed electrophysiological analysis and histological analysis. As a result, hiPSC-derived neurons expressed the sodium channel and showed the spontaneous firing of nerves. Additionally, to induce the neuron that are more closely similar to auditory nerve, we examined induction method of otic progenitors which generate inner ear nerves and confirmed expression of some markers for otic progenitor in induced cells.

Academic Significance and Societal Importance of the Research Achievements

本研究で確立されたヒトiPS細胞と内耳組織の共培養モデルとXPA患者由来神経幹細胞、神経細胞を用いることにより、XPA KOマウスでは不可能であった、XPA患者の神経変性モデルを作成することが可能になり、XPA患者における難聴発症メカニズムや治療法の検証に役立てることができる。また、ヒトiPS細胞由来内耳前駆細胞を介して内耳神経を誘導して共培養モデルに用いることにより、生体内耳に近いモデルの作出が可能なる。これにより神経変性のメカニズムが明らかになれば、感音性難聴だけでなくXPA患者における神経症状全般への治療の糸口になると予想され、本研究の社会的意義は高いと考えられる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2019 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Regenerative therapy for vestibular disorders using human induced pluripotent stem cells (iPSCs): neural differentiation of human iPSC-derived neural stem cells after in vitro transplantation into mouse vestibular epithelia.2016

    • Author(s)
      Taura A, Nakashima N, Ohnishi H, Nakagawa T, Funabiki K, Ito J, Omori K.
    • Journal Title

      Acta Otolaryngol.

      Volume: 136(10) Issue: 10 Pages: 999-1005

    • DOI

      10.1080/00016489.2016.1183169

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 「前庭障害に対するiPS細胞移植の可能性」2016

    • Author(s)
      田浦晶子 大西弘恵
    • Journal Title

      月刊 臨床神経科学 Clinical neurosciense

      Volume: 34 Pages: 1142-1144

    • Related Report
      2016 Research-status Report
  • [Journal Article] Transplantation of neurons derived from human iPS cells cultured on collagen matrix into guinea pig cochleae.2016

    • Author(s)
      Ishikawa M*, Ohnishi H*, Skerleva D, Sakamoto T, Yamamoto N, Hotta A, Ito J, Nakagawa T.
    • Journal Title

      J Tissue Eng Regen Med.

      Volume: in press Issue: 6 Pages: 1-13

    • DOI

      10.1002/term.2072

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Trial for Improvement of Hair Cell Induction Method from Human Induced Pluripotent Stem Cell.2019

    • Author(s)
      Ohnishi H, Skerleva D, Okuyama H, Miyamoto T, Matsuura S, Kirino K, Yamamoto N, Ito J, Omori K, Saito M, Tsukita K, Inoue H and Nakagawa T.
    • Organizer
      Association for Research in Otolaryngology 42th MidWinter Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞からの内耳有毛細胞誘導法改良の試み2019

    • Author(s)
      大西 弘恵、デシスラヴァ スケルレヴァ、奥山 英晃、宮本 達雄、松浦 伸也、桐野 浩輔、山本 典生、伊藤 壽一、大森 孝一、齋藤 潤、月田 香代子、井上 治久、中川 隆之.
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞から内耳有毛細胞様細胞を誘導するための段階的分化誘導法の検討2016

    • Author(s)
      大西 弘恵、Desislava Skerleva、北尻 真一郎、坂本 達則、山本 典生、伊藤 壽一、中川 隆之
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Book] 「iPS細胞の安全・高品質な作製技術、第6章, 第4節 ヒトiPS細胞からの前庭神経節細胞作製の開発」2016

    • Author(s)
      田浦晶子、大西弘恵
    • Total Pages
      494
    • Publisher
      株式会社 技術情報協会
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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