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Development of a new treatment method for hearing loss by fusing cochlear implant technology and cochlear nerve regeneration

Research Project

Project/Area Number 20K20307
Project/Area Number (Other) 17H06277 (2017-2019)
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund (2020)
Single-year Grants (2017-2019)
Research Field Surgery related to the biological and sensory functions and related fields
Research InstitutionResearch Institute, Shiga Medical Center

Principal Investigator

ITO JUICHI  滋賀県立総合病院(研究所), その他部局等, 特任上席研究員 (90176339)

Co-Investigator(Kenkyū-buntansha) 西村 幸司  京都大学, 医学研究科, 助教 (20405765)
扇田 秀章  滋賀県立総合病院(研究所), その他部局等, 専門研究員 (20761274)
大西 弘恵  京都大学, 医学研究科, 研究員 (50397634)
山本 典生  京都大学, 医学研究科, 准教授 (70378644)
田浦 晶子  藍野大学, 医療保健学部, 教授 (70515345)
松本 昌宏  滋賀県立総合病院(研究所), その他部局等, 専門研究員 (80773811)
Project Period (FY) 2017-06-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords人工内耳 / 蝸牛神経 / 再生 / ヒト多能性幹細胞(iPS) / 細胞移植 / 難聴 / 内耳 / 光刺激人工内耳 / iPS細胞移植 / ロボット手術 / オルガノイド / 聴神経 / 有毛細胞 / iPS / チャンネルロドプシン / 蝸牛神経(聴神経)( / ラセン神経節細胞 / ヒト多能性幹細胞(iPS細胞) / iPS細胞由来神経前駆細胞 / 聴神経(ラセン神経節細胞) / 間葉系幹細胞(MSC) / 聴力再生 / 蝸牛有毛細胞 / チャネルロドプシン / 再生医学 / トランスレーショナルリサーチ
Outline of Research at the Start

難聴は人口の高齢化に伴い、認知症との関連もあり、世界的な大問題となっている。しかし、内耳感覚細胞、ラセン神経節細胞の障害に起因する「感音難聴」は薬物治療は不可で、補聴器、人工内耳などの機器による聴覚補償が唯一の方法である。本研究では、再生医学を利用し、細胞移植による内耳細胞の再生と人工内耳の組み合わせで、難聴を克服させようとする計画である。特に移植細胞にはヒト人工多能性幹細胞を用い、人工内耳からの刺激には既存の電気刺激に加え、光ファイバーによる光刺激を用いることに新規性がある。

Outline of Final Research Achievements

The purpose of this study is to develop a new treatment method for people with advanced hearing loss by fusing novel cochlear implant technology and cochlear nerve regeneration technology. The following research was performed. 1) We created a deaf animal model that simulates the pathological condition of a patient with advanced sensorineural hearing loss. 2) Cochlear nerve progenitor cells, which are the source of transplanted cells, were induced from human iPS cells (hiPSCs). 3) hiPSCs induced neural progenitor cells were transplanted into the cochlea of deaf animals. Then we confirmed cochlear nerve regeneration and auditory function recovery using electrophysiological and histological methods. 4) The channel-rhodopsin gene was introduced into the transplanted cells and stimulation from the cochlear implant was performed by light instead of electricity, and it was verified whether good hearing could be obtained.

Academic Significance and Societal Importance of the Research Achievements

難聴に悩む人は世界人口の約5%であり、65 歳以上の3分の1が中等度難聴以上の難聴を抱えている。特に、高度難聴感音難聴者は治療不可であったが人工内耳が臨床応用されるに至り、世界中でこれまで40万人以上の高度感音難聴者が人工内耳の恩恵を受けている。人工内耳は優れた機器ではあるが、人工内耳を装着しても正常な聴力を獲得できるわけではない。本研究では人工内耳技術と蝸牛神経再生技術の融合による新規難聴治療法の開発のための基礎研究を行う。本研究の発想は申請者独自のものであり、学術的意義は大である。また、本研究が完成すれば、多くの難聴者がより良い聴力を獲得できることが期待され、社会的意義は大きい。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (38 results)

All 2022 2021 2020 2019 2018 2017 2016

All Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 8 results) Presentation (23 results) (of which Int'l Joint Research: 16 results,  Invited: 12 results)

  • [Journal Article] Variants of benign paroxysmal positional vertigo in relation to head position during sleep2022

    • Author(s)
      Shigeno Kohichiro、Ogita Hideaki、Funabiki Kazuo
    • Journal Title

      Journal of Vestibular Research

      Volume: 32 Issue: 1 Pages: 39

    • DOI

      10.3233/ves-180616

    • URL

      https://localhost/en/publications/056aa5c1-68da-4a88-8b51-dd7aa890721a

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor 1 promotes the extension of Tracheal Epithelium in an in Vitro Tracheal organ culture model2021

    • Author(s)
      Kishimoto Ippei、Ohnishi Hiroe、Yamahara Kohei、Nakagawa Takayuki、Yamashita Masaru、Omori Koichi、Yamamoto Norio
    • Journal Title

      Auris Nasus Larynx

      Volume: 48 Issue: 3 Pages: 441-450

    • DOI

      10.1016/j.anl.2020.09.017

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 小児の両側人工内耳装用効果 日本における二側目の手術時期と両側装用の意義2021

    • Author(s)
      森 尚彫, 山口 忍, 石田 愛, 近藤 香菜子, 岡野 高之, 伊藤 壽一, 大森 孝一, 山本 典生
    • Journal Title

      日本耳鼻咽喉科頭頸部外科学会会報

      Volume: 124 Pages: 1664-1665

    • NAID

      130008139510

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In silico analysis of inner ear development using public whole embryonic body single-cell RNA-sequencing data.2021

    • Author(s)
      Yamamoto R, Ohnishi H, Omori K, Yamamoto N
    • Journal Title

      Dev Biol

      Volume: 469 Pages: 160-171

    • DOI

      10.1016/j.ydbio.2020.10.009

    • NAID

      120006938956

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of bilateral cochlear implants in children: Timing of second surgery and the significance of wearing bilateral cochlear implants in Japan.2020

    • Author(s)
      Mori N, Yamaguchi S, Ishida A, Kondo K, Okano T, Ito J, Omori K, and Yamamoto N
    • Journal Title

      Auris Nasus Larynx

      Volume: 47 Issue: 3 Pages: 359-366

    • DOI

      10.1016/j.anl.2019.11.001

    • NAID

      130008139510

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin-Like Growth Factor 1 on the Maintenance of Ribbon Synapses in Mouse Cochlear Explant Cultures2020

    • Author(s)
      Gao Li、Kita Tomoko、Katsuno Tatsuya、Yamamoto Norio、Omori Koichi、Nakagawa Takayuki
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 14 Pages: 571155-571155

    • DOI

      10.3389/fncel.2020.571155

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model2020

    • Author(s)
      Matsunaga Mami、Kita Tomoko、Yamamoto Ryosuke、Yamamoto Norio、Okano Takayuki、Omori Koichi、Sakamoto Satoko、Nakagawa Takayuki
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 14 Pages: 583994-583994

    • DOI

      10.3389/fncel.2020.583994

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIOBP-5 sculpts stereocilia rootlets and stiffens supporting cells enabling hearing2019

    • Author(s)
      Katsuno Tatsuya、Belyantseva Inna A.、Cartagena-Rivera Alexander X.、Ohta Keisuke、Crump Shawn M.、Omori Koichi、Ito Juichi、Frolenkov Gregory I.、Friedman Thomas B.、Kitajiri Shin-ichiro
    • Journal Title

      JCI Insight

      Volume: 4 Issue: 12 Pages: 1-21

    • DOI

      10.1172/jci.insight.128561

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hearing preservation at low frequencies by insulin-like growth factor 1 in a guinea pig model of cochlear implantation.2018

    • Author(s)
      Yamahara K, Nishimura K, Ogita H, Ito J, Nakagawa T, Furuta I, Kita T, Omori K, Yamamoto N.
    • Journal Title

      Hear Res.

      Volume: 368 Pages: 92-108

    • DOI

      10.1016/j.heares.2018.07.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Netrin 1 mediates protective effects exerted by insulin-like growth factor 1 on cochlear hair cells.2017

    • Author(s)
      Yamahara K, Nakagawa T, Ito J, Kinoshita K, Omori K, Yamamoto N.
    • Journal Title

      Neuropharmacology.

      Volume: 119 Pages: 26-39

    • DOI

      10.1016/j.neuropharm.2017.03.032

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microarray analyses of otospheres derived from the cochlea in the inner ear identify putative transcription factors that regulate the characteristics of otospheres.2017

    • Author(s)
      Iki T, Tanaka M, Kitajiri SI, Kita T, Kawasaki Y, Mizukoshi A, Fujibuchi W, Nakagawa T, Nakahata T, Ito J, Omori K, Saito MK.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 6 Pages: e0179901-e0179901

    • DOI

      10.1371/journal.pone.0179901

    • NAID

      120006782202

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative Analysis of Aquaporin Expression Levels during the Development and Maturation of the Inner Ear2017

    • Author(s)
      Miyoshi, T. Yamaguchi, T. Ogita, K. Tanaka, Y. Ishibashi, K. I. Ito, H. Kobayashi, T. Nakagawa, T. Ito, J. Omori, K. Yamamoto, N.
    • Journal Title

      J Assoc Res Otolaryngol

      Volume: 18 Issue: 2 Pages: 247-261

    • DOI

      10.1007/s10162-016-0607-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histopathological evaluation and long-term results of soft tissue preservation technique in cholesteatoma surgery2017

    • Author(s)
      Hiraumi H., Kanemaru S. I., Miura M., Yamamoto N., Sakamoto T., and Ito J
    • Journal Title

      Eur Arch Otorhinolaryngol

      Volume: 274 Issue: 2 Pages: 711-714

    • DOI

      10.1007/s00405-016-4328-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 人工聴覚器-人工内耳のトピック、聴力温存と蝸牛構造温存 新規人工聴覚器(人工聴覚上皮)の開発 HIBIKIプロジェクト2017

    • Author(s)
      伊藤壽一
    • Journal Title

      Otol Jpn

      Volume: 27 Pages: 671-676

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [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
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 耳科学の進歩 蝸牛神経の基礎研究 隠れ難聴の病態解明と再生研究.2021

    • Author(s)
      西村幸司
    • Organizer
      第122回日本耳鼻咽喉科学会・学術講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] A New Type of a Cochlear Implant With Piezoelectric Membrane. .2021

    • Author(s)
      Hideaki Ogita, Koji Nishimura, Takayuki Nakagawa, Juichi Ito
    • Organizer
      The 44th annual midwinter research meeting of the Association for Research in Otolaryngology.
    • Related Report
      2020 Research-status Report
  • [Presentation] 内耳再生とその臨床応用の展望2020

    • Author(s)
      伊藤壽一
    • Organizer
      第30回日本耳科学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 新しい蝸牛軸近接型人工内耳電極の使用経験2020

    • Author(s)
      伊藤壽一、扇田秀章、松本昌宏
    • Organizer
      第121回日本耳鼻咽喉科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Slim Modiolar 電極(CI 532)使用経験2020

    • Author(s)
      伊藤壽一
    • Organizer
      岩手医科大学側頭骨実習人工内耳イブニングセミナー
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Cochlear Implants Meet Regeneration of Primary Auditory Neurons2020

    • Author(s)
      西村幸司
    • Organizer
      第30回日本耳科学会、
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Robotic insertion of new cochlea implants.2020

    • Author(s)
      Hideaki Ogita, Juichi Ito, Koji Nishimura, Takayuki Nakagawa, Tetsuro Tsuji, Satoyuki Kawano, Hidetoshi Kotera, Takeshi Nizuka, Masanori Enrin, Hisakazu Ninomiya.
    • Organizer
      ARO 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The future of cochlear implant.2019

    • Author(s)
      Juichi Ito
    • Organizer
      COSM2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hearing recovery by a totally implantable artificial auditory epithelium in the guinea pig cochlea.2019

    • Author(s)
      Juichi Ito
    • Organizer
      CORLAS Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Engraftment of human induced pluripotent stem cells and guinea pig bone marrow-derived stem cells into the cochlea of guinea pig.2019

    • Author(s)
      Juichi Ito
    • Organizer
      IEB 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The transplantation of sphere-forming stem cells from the inner ear into cochlea.2019

    • Author(s)
      Hideaki Ogita, Juichi Ito, Koji Nishimura, Hiroe Ohnishi, Akiko Taura
    • Organizer
      IEB 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Improvement of otic induction from human induced pluripotent stem cell.2019

    • Author(s)
      Hiroe Ohnishi, Juichi Ito, Norio Yamamoto, Koichi Omori, Takayuki Nakagawa
    • Organizer
      IEB 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Platinum Black Plating Decreases the Impedance for Cochlear Implants to Stimulate Auditory Neurons.2018

    • Author(s)
      Ogita H, Nishimura K, Ito J.
    • Organizer
      41th ARO
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The development of a newly invented inner ear implant device2018

    • Author(s)
      Ito J, Ogita H, Nishimura K.
    • Organizer
      31th Politzer Society Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Future Development of Inner Ear Implant2018

    • Author(s)
      Ito J
    • Organizer
      10th International Academic Conference in Otology, Rhinology and Laryngology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The development of a Newly Invented Inner Ear Implant Device2018

    • Author(s)
      Ito J
    • Organizer
      31st Politzer Society Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regenerative medicine for vestibular disorders2017

    • Author(s)
      Ito J
    • Organizer
      ARO
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Round table: State of art treatments in Meniere’desease2017

    • Author(s)
      Ito J
    • Organizer
      IFOS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Use of in situ therapies such as insulin-like growth factor-1 (IGF-1) for treatment of sudden SNHL2017

    • Author(s)
      Ito J
    • Organizer
      IFOS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] New local drug delivery system to the inner ear using insulin-like growth factor-1 (IGF-1) for treatment of sudden sensorineural hearing loss (SSNHL)2017

    • Author(s)
      Ito J
    • Organizer
      IFOS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The Future of Inner Ear Implant2017

    • Author(s)
      Ito J
    • Organizer
      IFOS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] めまい平衡医学の解剖と生理2017

    • Author(s)
      伊藤壽一
    • Organizer
      第34回 日本めまい平衡医学会医師講習会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] New local drug delivery system to the inner ear using insulin-like growth factor-1 (IGF-1) for treatment of sudden sensorineural hearing loss (SSNHL)2017

    • Author(s)
      Ito J
    • Organizer
      4th Congress of European ORL-HNS
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2017-07-21   Modified: 2024-12-25  

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