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Generation of inner ear hair cells toward cell transplantation using pluripotent stem cells

Research Project

Project/Area Number 16H05482
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNara Medical University

Principal Investigator

Yoshikawa Masahide  奈良県立医科大学, 医学部, 教授 (50230701)

Co-Investigator(Kenkyū-buntansha) 北原 糺  奈良県立医科大学, 医学部, 教授 (30343255)
王寺 幸輝  奈良県立医科大学, 医学部, 准教授 (50343421)
和中 明生  奈良県立医科大学, 医学部, 教授 (90210989)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords内耳 / 再生医学 / 有毛細胞 / 幹細胞 / 耳科学 / 分化誘導 / 細胞培養 / 聴覚再生 / 難聴疾患 / ES細胞 / マウス / 転写因子 / 細胞移植 / iPS細胞 / 内耳再生
Outline of Final Research Achievements

The self-renewal capability of inner ear hair cells in mammals is extremely poor, thus stem cells harboring an ability to generate inner ear hair cells is a promising treatment option for damaged inner ear hair cells. We have successfully developed a new method for in vitro production of inner hair cells from pluripotent stem cells. In the present study, the mechanism of differentiation and possibility of cell transplantation using isolated cochlea tissue samples were investigated. The results showed that secretory factors related to resident cells in the inner ear facilitated differentiation of stem cells into inner ear hair cells, with several candidates determined based on RNA-sequence analysis. In addition, analysis of the co-culture with embryonic stem cell-derived inner ear hair cells and isolated cochlea tissues revealed cell settlement in the cochlea, suggesting the applicability of this in vivo method for cell transplantation therapy.

Academic Significance and Societal Importance of the Research Achievements

難聴治療の鍵となる内耳有毛細胞に着目し、様々な細胞に分化可能な多能性幹細胞から効率良く誘導する方法を開発した。本法は、これまでの方法に比べ簡便かつ高効率である。内耳細胞の再生研究および細胞移植治療に用いる細胞源確保に十分貢献できる成果である。本研究で開発した手法を、臨床応用が開始されたヒトiPS細胞へ適応することで、今後の耳科領域における研究を更に発展させる可能性がある。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (38 results)

All 2020 2019 2018 2017 2016

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 3 results) Book (6 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
  • [Journal Article] Isolation and culture of pleural mesothelial cells2019

    • Author(s)
      Kawai N, Ouji Y, Sakagami M, Tojo T, Sawabata N, Yoshikawa M, Taniguchi S.
    • Journal Title

      Exp Lung Res

      Volume: 45 Issue: 5-6 Pages: 151-156

    • DOI

      10.1080/01902148.2018.1511002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of cross-linked gelatin glue in canine lung surgery models2019

    • Author(s)
      Kawai No, Suzuki S, Yamashita K, Niwa K, Tojo T, Sawabata N, Nakai T, Ouji Y, Yoshikawa M, Ikada Y, Taniguchi S
    • Journal Title

      J Nara Med Assoc

      Volume: 70 Pages: 35-43

    • NAID

      120006892014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ここまで進んだ再生医学 多能性幹細胞から内耳有毛細胞への分化誘導法も含めて2019

    • Author(s)
      吉川正英
    • Journal Title

      耳鼻咽喉科ニューロサイエンス

      Volume: 33 Pages: 1-5

    • Related Report
      2019 Annual Research Report
  • [Journal Article] インド帰国後の亜急性下痢、腹痛からセイロン鉤虫症と診断し、治療した症例2019

    • Author(s)
      宮里悠佑, 大場雄一郎, 吉川正英
    • Journal Title

      Clinical Parasitolog

      Volume: 30 Pages: 113-115

    • Related Report
      2019 Annual Research Report
  • [Journal Article] アニサキス亜科線虫第4期幼虫感染の16例について2019

    • Author(s)
      山田稔, 畑中秀亮, 石井明, 吉川正英
    • Journal Title

      Clinical Parasitolog

      Volume: 30 Pages: 74-76

    • Related Report
      2019 Annual Research Report
  • [Journal Article] タイ帰国後に無鉤条虫を認めた1例2019

    • Author(s)
      平位暢康, 三須政康, 王寺幸輝,笠松丈人, 吉原真吾, 古川龍太郎, 西村知子, 奥田菜緒, 今北菜津子, 福盛達也, 小川拓, 笠原敬, 佐藤公俊, 前田光一, 三笠桂一, 吉川正英, 山崎浩, 森嶋康之
    • Journal Title

      Clinical Parasitolog

      Volume: 30 Pages: 43-45

    • Related Report
      2019 Annual Research Report
  • [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: in press

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of covering with cross-linked gelatin glue on tissue regeneration in a rat lung injury model.2019

    • Author(s)
      Kawai N, Suzuki S, Ouji Y, Takeda M, Sakagami M, Tojo T, Sawabata N, Yoshikawa M, Ikada Y, Taniguchi S.
    • Journal Title

      Interact Cardiovasc Thorac Surg.

      Volume: ivy297 Issue: 1 Pages: 1-7

    • DOI

      10.1093/icvts/ivy297

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of lung-like cells from mouse embryonic stem cells by decellularized lung matrix.2018

    • Author(s)
      Kawai N, Ouji Y, Sakagami M, Tojo T, Sawabata N, Yoshikawa M, Taniguchi S.
    • Journal Title

      Biochem Biophys Rep.

      Volume: 15 Pages: 733-738

    • DOI

      10.1016/j.bbrep.2018.06.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations.2018

    • Author(s)
      Hirai N, Kasahara K, Fujikura H, Yoshihara S, Ogawa T, Ogawa Y, Hishiya N, Suzuki Y, Nakano R, Yano H, Yoshikawa M, Mikasa K.
    • Journal Title

      J Infect Chemother.

      Volume: 24 Issue: 7 Pages: 570-572

    • DOI

      10.1016/j.jiac.2017.12.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea.2018

    • Author(s)
      Yoshikawa M, Ouji Y, Hirai N, Nakamura-Uchiyama F, Yamada M, Arizono N, Akamatsu N, Yoh T, Kaya D, Nakatani T, Kikuchi E, Katanami Y, Satoh K, Maki R, Miyazato Y, Oba Y, Kasahara K, Mikasa K.
    • Journal Title

      Trop Med Health

      Volume: 46 Issue: 1 Pages: 1-8

    • DOI

      10.1186/s41182-018-0087-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient induction of inner ear hair cell-like cells from mouse ES cells using combination of Math1 transfection and conditioned medium from ST2 stromal cells.2017

    • Author(s)
      Ouji Y, Sakagami M, Omori H, Higashiyama S, Kawai N, Kitahara T, Wanaka A, Yoshikawa M.
    • Journal Title

      Stem Cell Research

      Volume: 23 Pages: 50-56

    • DOI

      10.1016/j.scr.2017.06.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells in human glioblastoma in vitro and in vivo.2016

    • Author(s)
      Nakazawa T, Nakamura M, Matsuda R, Nishimura F, Park YS, Motoyama Y, Hironaka Y, Nakagawa I, Yokota H, Yamada S, Tamura K, Takeshima Y, Omoto K, Tanaka Y, Ouji Y, Yoshikawa M, Tsujimura T, Nakase H.
    • Journal Title

      J Neurooncol

      Volume: 129 Issue: 2 Pages: 231-241

    • DOI

      10.1007/s11060-016-2186-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ancylostoma ceylanicum hookworm infection in Japanese traveler who presented chronic diarrhea after return from Lao People's Democratic Republic.2016

    • Author(s)
      Kaya D, Yoshikawa M, Nakatani T, Tomo-Oka F, Fujimoto Y, Ishida K, Fujinaga Y, Aihara Y, Nagamatsu S, Matsuo E, Tokoro M, Ouji Y, Kikuchi E.
    • Journal Title

      Parasitol Int.

      Volume: 65 Issue: 6 Pages: 737-740

    • DOI

      10.1016/j.parint.2016.07.001

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 便検査を繰り返し施行することで診断に至ったランブル鞭毛虫症の一例2020

    • Author(s)
      村上紘一, 久保貴裕, 中谷敏也, 加知宏規, 尾山雅文, 元川雄貴, 森仁志, 芝本彰彦, 相原洋祐, 永松晋作, 上嶋昌和, 松尾英城, 菊池英亮, 吉川正英
    • Organizer
      日本消化器病学会近畿支部例会
    • Related Report
      2019 Annual Research Report
  • [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、河合紀和、吉川正英、北原糺
    • Organizer
      第19回 日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [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、吉川正英、北原糺
    • Organizer
      第28回日本耳科学会 総会・学術講演
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄炎で発症し肺肝病変を伴ったトキソカラ症の1例2018

    • Author(s)
      井口直彦、形岡博史、正畠良悟、桐山敬生、吉川正英、杉江和馬
    • Organizer
      第23回日本神経感染症学会総会・学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characterization of murine hair follicle stem cells under long-term culture conditions2018

    • Author(s)
      Ouji Y, Kawai N, Sakagami M, Yoshikawa M.
    • Organizer
      16th International Society for Stem Cell Research Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Differentiation of mouse embryonic stem cells into inner ear cell-like cells using vestibular cell-conditioned medium.2018

    • 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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 消化管に一隻のイヌ鉤虫が発見された日本在住のブラジル人症例2018

    • Author(s)
      赤松尚明、吉川正英、山田稔、楊孝治、平位暢康、王寺幸輝、有薗直樹
    • Organizer
      第29回 日本臨床寄生虫学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of vestibular cell-conditioned medium on differentiation of embryonic stem cells into inner ear vestibular hair cells2018

    • Author(s)
      Sakagami M, Ouji Y, Kawai N, Kitahara T, Yoshikawa M.
    • Organizer
      41st Annual MidWinter Meeting, Association for research in otolaryngology (ARO)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 長期培養維持した毛包上皮幹細胞のキャラクタリゼーション2018

    • Author(s)
      王寺幸輝、河合紀和、阪上雅治、吉川正英
    • Organizer
      第17回 日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ES細胞から分化誘導した内耳有毛細胞のキャラクタリゼーション2017

    • Author(s)
      阪上雅治、王寺幸輝、河合紀和、北原糺、吉川正英
    • Organizer
      第16回 日本再生医療学会総会
    • Place of Presentation
      仙台国際線センター(仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 皮膚上皮幹細胞の長期培養条件の検討とWntシグナル2017

    • Author(s)
      王寺幸輝、河合紀和、阪上雅治、三須政康、吉川正英
    • Organizer
      第16回 日本再生医療学会総会
    • Place of Presentation
      仙台国際線センター(仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 無細胞化マトリックスを用いたES細胞から肺細胞への効率的分化誘導法の開発2017

    • Author(s)
      河合紀和、王寺幸輝、阪上雅治、東条尚、谷口繁樹、吉川正英
    • Organizer
      第16回 日本再生医療学会総会
    • Place of Presentation
      仙台国際線センター(仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] ES細胞から分化誘導した内耳有毛細胞のキャラクタリゼーション2017

    • Author(s)
      阪上雅治、吉川正英、北原糺
    • Organizer
      第27回 日本耳科学会総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Maintenance and long-term expansion of murine skin epithelial stem cells by Wnt signaling pathway2017

    • Author(s)
      Ouji Y, Sakagami M, Kawai N, Yoshikawa M.
    • Organizer
      10th World Congress for Hair Research 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] セイロン鉤虫症は海外渡航時に注意すべき感染症であるー日本人4症例の検討ー2017

    • Author(s)
      吉川正英、王寺幸輝、中村ー内山ふくみ、有薗直樹、山田稔、赤松尚明、賀屋大介、片浪雄一、眞木良祐、大場雄一郎
    • Organizer
      第58回 日本熱帯医学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 2009年にマレーシアにて感染したセイロン鉤虫症例 海外感染した日本人の同症第一確定例2017

    • Author(s)
      赤松尚明、山田稔、有薗直樹、楊孝治、王寺幸輝、吉川正英
    • Organizer
      第28回 日本臨床寄生虫学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 奈良医大感染症センター寄生虫専門外来10年の経験2017

    • Author(s)
      平位暢康、吉川正英、中村ふくみ、王寺幸輝、今井雄一郎、藤倉裕之、吉井誠也、吉原真吾、今北菜津子、小川拓、小川吉彦、米川真輔、平田一記、菱矢直邦、梶田明裕、白石直敬、佐藤公俊、福森達也、辻本和徳、中川智代、宇野健司、笠原敬、前田光一、古西満、武山雅博、大西智子、片浪雄一、忽那賢志、三笠桂一
    • Organizer
      第28回 日本臨床寄生虫学会大会
    • Related Report
      2017 Annual Research Report
  • [Book] 消化器内視鏡 【消化管感染症のすべて】十二指腸-小腸 寄生虫感染症 鉤虫症2019

    • Author(s)
      松尾英城, 吉川正英, 賀屋大介, 菊池英亮
    • Total Pages
      3
    • Publisher
      東京医学社
    • ISBN
      9784885636264
    • Related Report
      2019 Annual Research Report
  • [Book] 小児科、小児寄生虫感染症の対策・予防2018

    • Author(s)
      吉川正英、沢田敦、間瀬史絵、平位暢康、大西智子、武山雅博、笠原敬、王寺幸輝
    • Total Pages
      14
    • Publisher
      金原出版
    • Related Report
      2018 Annual Research Report
  • [Book] 日常検査で役立つ寄生虫・原虫検出法 抗原・抗体反応を利用した寄生虫検査2017

    • Author(s)
      王寺幸輝、吉川正英
    • Total Pages
      6
    • Publisher
      Medical Technology
    • Related Report
      2017 Annual Research Report
  • [Book] Induction of Inner Ear Hair Cells from Mouse Embryonic Stem Cells In Vitro.2016

    • Author(s)
      Yoshikawa M, Ouji Y.
    • Total Pages
      11
    • Publisher
      Methods Mol Biol
    • Related Report
      2016 Annual Research Report
  • [Book] Maintenance of Skin Epithelial Stem Cells by Wnt-3a In Vitro.2016

    • Author(s)
      Ouji Y, Yoshikawa M.
    • Total Pages
      10
    • Publisher
      Methods Mol Biol
    • Related Report
      2016 Annual Research Report
  • [Book] Maintenance of Dermal Papilla Cells by Wnt-10b In Vitro.2016

    • Author(s)
      Ouji Y, Yoshikawa M.
    • Total Pages
      9
    • Publisher
      Methods Mol Biol
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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