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Drug screening and development using hES/iPSC-derived otic progenitor

Research Project

Project/Area Number 26670748
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Otorhinolaryngology
Research InstitutionKeio University

Principal Investigator

Ogawa Kaoru  慶應義塾大学, 医学部(信濃町), 教授 (00169179)

Co-Investigator(Kenkyū-buntansha) 水足 邦雄  独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 医師 (40338140)
藤岡 正人  慶應義塾大学, 医学部(信濃町), 講師 (70398626)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords感音難聴 / iPS細胞 / 創薬研究 / 薬剤スクリーニング
Outline of Final Research Achievements

Since the inner ear is located deep inside the temporal bone and its biopsy causes severe hearing loss, studies using human inner ear cells have not been performed so far. In this study, we developed drug screening systems using a highly efficient inner otocyst-like cell induction method from hES/iPS cells. From the study, we obtained new hair cell inducers and a humoral factor for the induction of outer sulcus cells, defined a molecular mechanism of the maintenance of stemness in the cochlear progenitors and a mechanism for the maturation of hair cells. Also, we obtained the MABEL of rapamycin on the prevention of apoptosis of the outer sulcus cells of Pendred syndrome/ DFNB4.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (21 results)

All 2017 2016 2015 2014 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Cochlear Cell Modeling Using Disease-Specific iPSCs Unveils a Degenerative Phenotype and Suggests Treatments for Congenital Progressive Hearing Loss2017

    • Author(s)
      Makoto Hosoya, Masato Fujioka, Takefumi Sone, Satoshi Okamoto, Wado Akamatsu, Hideki Ukai, Hiroki R. Ueda, Kaoru Ogawa, Tatsuo Matsunaga, Hideyuki Okano
    • Journal Title

      Cell Reports

      Volume: 18 Issue: 1 Pages: 68-81

    • DOI

      10.1016/j.celrep.2016.12.020

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Manupilating cell-fate in the cochlea: a feasible therapy for hearing loss.2015

    • Author(s)
      Fujioka M, Okano H, Edge ASB
    • Journal Title

      Trends in Neuroscience

      Volume: 38 Issue: 3 Pages: 139-144

    • DOI

      10.1016/j.tins.2014.12.004

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] nflammatory and immuneresponses in the cochlea: potential therapeutic targets for sensorineural hearing loss2014

    • Author(s)
      Fujioka M, Okano H, Ogawa K.
    • Journal Title

      Flontiers in Pharmacology

      Volume: 12

    • DOI

      10.3389/fphar.2014.00287

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall: a potential therapeutic target for sensorineural hearing loss.2014

    • Author(s)
      Fujioka M, Okamoto Y, Shinden S, Okano HJ, Okano H, Ogawa K, Matsunaga T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e90089-e90089

    • DOI

      10.1371/journal.pone.0090089

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 両側進行性内耳性難聴の病態生理研究~疾患iPS創薬の立場から~2016

    • Author(s)
      藤岡正人・細谷誠・鈴木法臣・大石直樹・松崎佐栄子・小川郁
    • Organizer
      第26回日本耳科学会総会・学術講演会
    • Place of Presentation
      ホテル国際21(長野県長野市)
    • Year and Date
      2016-10-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Minding species gaps in the cochlea: non-human primate and patient derived- hiPSC models for the study of hereditary hearing loss2016

    • Author(s)
      藤岡正人
    • Organizer
      IEB 2016
    • Place of Presentation
      モンペリエ,フランス
    • Year and Date
      2016-09-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 母親にのみ新規<I>EYA4</I>遺伝子変異を認めた家族性難聴の1例2016

    • Author(s)
      藤岡正人・松永達雄・長谷部夏希・神崎晶・大石直樹・平賀良彦・鈴木法臣・松崎佐栄子・川浦光弘・小川郁
    • Organizer
      第78回耳鼻咽喉科臨床学会総会・学術講演会
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島市)
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cochlear disease modeling and drug discovery by using human iPSC-based technologies2016

    • Author(s)
      Masato Fujioka
    • Organizer
      16th Japan-Korea Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
    • Place of Presentation
      ハイアットリージェンシー東京(東京都新宿区)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Translating back and forth in between benchside and bedside by hiPS based-technology and a primate model (invited speaker)2015

    • Author(s)
      Masato Fujioka
    • Organizer
      The 13rd. Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery,
    • Place of Presentation
      一橋大学一橋講堂(東京都千代田区)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 再生医学的アプローチと幹細胞医学による内耳性難聴の研究2015

    • Author(s)
      藤岡 正人
    • Organizer
      日本耳科学会学術講演会・聴覚生理研究会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] MYO15A新規遺伝子変異症例からの疾患特異的iPS細胞の樹立と解析2015

    • Author(s)
      藤岡正人 細谷 誠・松永 達雄・小川 郁・岡野 栄之
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトES/iPS細胞をソースとした高純度内耳有毛細胞誘導系と人工蝸牛感覚上皮シート作成のこころみ2015

    • Author(s)
      藤岡正人、細谷 誠、小川 郁、岡野 栄之
    • Organizer
      第36回日本炎症・再生医学会ヒトES/iPS細胞をソースとした高純度内耳有毛細胞誘導系と人工蝸牛感覚上皮シート作成のこころみ
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
  • [Presentation] PENDRED症候群疾患特異的iPS細胞由来内耳細胞を用いた薬剤スクリーニング2015

    • Author(s)
      細谷 誠、藤岡 正人、岡本 理志、曽根 岳史、松永 達雄、赤松 和土、小川 郁、岡野 栄之
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都港区)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
  • [Presentation] PENDRED症候群疾患特異的iPS細胞由来内耳細胞を用いた薬剤スクリーニング2015

    • Author(s)
      細谷誠 藤岡 正人・松永 達雄・小川 郁
    • Organizer
      第116回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      国際フォーラム(東京都千代田区)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Presentation] 蝸牛感覚上皮の再生医療と幹細胞生物学的アプローチによる内耳疾患研究2015

    • Author(s)
      藤岡 正人, 細谷 誠, 渡部 孝太郎, 加我 君孝, 松永 達雄, 小川 郁
    • Organizer
      第14回再生医療学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-03-19
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 幹細胞・iPS細胞を用いた内耳性難聴の研究~新規治療法の開発に向けて~2015

    • Author(s)
      藤岡正人
    • Organizer
      第10回感覚器シンポジウム
    • Place of Presentation
      NHO東京医療センター講堂(東京都世田谷区)
    • Year and Date
      2015-03-06
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] MYO15A新規遺伝子変異症例からの疾患特異的iPS細胞の樹立2014

    • Author(s)
      藤岡 正人, 細谷 誠, 渡部 孝太郎, 加我 君孝, 松永 達雄, 小川 郁
    • Organizer
      日本耳科学会
    • Place of Presentation
      朱鷺メッセ(新潟県新潟市)
    • Year and Date
      2014-10-17
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞技術を用いた内耳疾患研究~有毛細胞再生から疾患特異的iPS研究まで~2014

    • Author(s)
      藤岡正人
    • Organizer
      東京都地方部会第41回総会・第203回学術講演会
    • Place of Presentation
      ホテルメトロポリタン池袋(東京都豊島区)
    • Year and Date
      2014-06-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 慶應義塾大学医学部耳鼻咽喉科学教室研究紹介

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 内耳性難聴治療薬2015

    • Inventor(s)
      細谷誠、藤岡正人、岡野栄之、小川郁、松永達雄
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-01-19
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] ヒト多能性幹細胞からの胚葉体を介さない内耳前駆細胞の効率的誘導および選択法とそれを用いた内耳細胞(組織幹細胞から分化細胞の誘導法、および本誘導法を利用した内耳細胞移植法と薬剤スクリーニング法2014

    • Inventor(s)
      細谷誠、藤岡正人、岡野栄之
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-05-13
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2021-01-27  

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