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Development of inner ear regenerative medicine using animal models for inner ear diseases

Research Project

Project/Area Number 17209054
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionKyoto University

Principal Investigator

ITO Juichi  Kyoto University, Graduate School of medicine, Professor (90176339)

Co-Investigator(Kenkyū-buntansha) TSUJI Jun  National Hospital Organization Kyoto Meclical Center, 政策医療企画研究部, Researcher (30252448)
NAKAGAWA Takayuki  KYOTO UNIVERSITY, Graduate School of medicine, Assistant Professor (50335270)
KOJIMA Ken  KYOTO UNIVERSITY, Graduate School of medicine, Researcher of COE (60378685)
HIRAUMI Harukazu  KYOTO UNIVERSITY, Graduate School of medicine, Assistant Professor (10374167)
MIURA Makoto  KYOTO UNIVERSITY, Graduate School of medicine, Lecturer (70263077)
藤野 清大  京都大学, 医学研究科, 助手 (50359832)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥49,790,000 (Direct Cost: ¥38,300,000、Indirect Cost: ¥11,490,000)
Fiscal Year 2007: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2006: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2005: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
KeywordsCell transplantation / hearing loss / spiral ligament / spiral ganglion / Bone marrow-derived stromal cell / Hematopoietic stem cell / Neural stem cells / ES cell / ラセン靭帯 / 胚性幹細胞 / 骨髓由来細胞 / 有毛細胞 / ラセン神経節細胞 / 幹細胞 / 骨髄間葉系細胞 / 神経栄養因子
Research Abstract

The aim of this project was to establish animal models of inner ear degeneration as the hack of fixture clinical application. We used four animal models in this project, a mouse model for degeneration of the spiral ligament, a mouse model for age-related hearing loss, a rat model for degeneration of the cochlear nerve and a guinea pig model for degeneration of the spiral ganglion. We have established a mouse model for degeneration of the spiral ligament, which shows selective degeneration of spiral ligament fibrocytes and loss of the endocochlear potential Transplantation of bone marro-derived stromal cells results in functional recovery of the endocochlear potential. Studies on a model for age-related hearing loss have revealed roles of hematopoietic stem rills in age related hearing has Studies on a model for degeneration of the cochlear nerve have demonstrated the potential of spiral ganglion neuron-derived cells for regeneration of the cochlear nerve. Studies on a model for degeneration of the spiral ganglion have demonstrated the functional restoration of spiral ganglions by transplantation of ES cell-derived neural progenitors. These findings demonstrate the feasibility of a cell transplantation approach for inner ear regeneration in humans.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (47 results)

All 2008 2007 2006 2005 Other

All Journal Article (20 results) (of which Peer Reviewed: 5 results) Presentation (21 results) Book (5 results) Remarks (1 results)

  • [Journal Article] Replacement of diseased auditory neurons by cell transplantation.2008

    • Author(s)
      Sekiya T, Kojima K, Matsumoto M, et. al.
    • Journal Title

      Front Biosci. 13

      Pages: 2165-76

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Replacement of diseased auditory neurons by cell transplantation2008

    • Author(s)
      Sekiya, T., Kojima, K., Matsumoto, M., et. al.
    • Journal Title

      Front Biosci 13, 21

      Pages: 65-76

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow-derived cells expressing Ibal are constitutively present as resident tissue macrophages in the mouse cochlea.2008

    • Author(s)
      Okano T, Nakagawa T, Kita T, Kada S, Yoshimoto M, Nakahata T, Ito J.
    • Journal Title

      J Neurosci Res (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The potential use of bone marrow stromal cells for cochlear cell therapy.2007

    • Author(s)
      Sharif S, Nkagawa T, Ohno T, et. al.
    • Journal Title

      Neuroreport 8

      Pages: 352-354

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The potential use of bone marrow stromal cells for cochlear cell therapy.2007

    • Author(s)
      Sharif S, Nakagawa T, Ohno T et al.
    • Journal Title

      Neuroreport 8・4

      Pages: 352-354

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transplantation of conditionally immortal auditory neuroblasts to the auditory nerve.2007

    • Author(s)
      Sekiya T, Holley M, Kojima K et al.
    • Journal Title

      Eur J Neurosci (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rebuilding lost hearing using cell transplantation.2007

    • Author(s)
      Sekiya T, Kojima K, Matsumoto M et al.
    • Journal Title

      Neurosurgery 60・3

      Pages: 417-433

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distribution of GFP expressing cells in the developing inner ear of pHesl- or pHes5-d2EGFP transgenic mouse.2006

    • Author(s)
      Kojima K, Takebayashi S, Matsumoto M et al.
    • Journal Title

      Neuroscience Res 55:Suppl:143

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell transplantation to the auditory nerve and cochlear duct.2006

    • Author(s)
      Sekiya T, Kojima K, Matsumoto M et al.
    • Journal Title

      Exp Neurol 198

      Pages: 12-24

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell-Gene Delivery of Brain-Derived Neurotrophic Factor to the Mouse Inner Ear.2006

    • Author(s)
      Okano T, Nakagawa T, Kita T et al.
    • Journal Title

      Mol Ther 14・6

      Pages: 866-871

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell therapy for inner ear diseases.2005

    • Author(s)
      Nakagawa T, Ito J.
    • Journal Title

      Curr Pharm Des 11・9

      Pages: 1203-1207

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Elevation of superoxide dismutase increases acoustic trauma from noise exposure.2005

    • Author(s)
      Endo T, Nakagawa T, Iguchi F, Kita T, Okano T, Sha SH, Schacht J, Shiga A, Kim TS, Ito J.
    • Journal Title

      Free Rad Biol Med 38・4

      Pages: 492-498

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel strategy for treatment of inner ears using a biodegradable gel.2005

    • Author(s)
      Endo T, Nakagawa t, Kita T, Iguchi F, Kim TS, Tamura T, Iwai K, Tabata Y, Ito J.
    • Journal Title

      Laryngoscope 115・11

      Pages: 2016-2020

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neural connections between embryonic stem cell-derived neurons and vestibular hair cells in vitro.2005

    • Author(s)
      Kim TS, Nakagawa T, Kita T, Higashi T, Takebayashi S, Matsumoto M, Kojima K, Sakamoto T, Ito J
    • Journal Title

      Brain Res 1057・1-2

      Pages: 127-133

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Disruption and restoration of cell-cell junctions in mouse vestibular epithelia following aminoglycoside treatment.2005

    • Author(s)
      Kim TS, Nakagawa T, Kitajiri S, Endo T, Takebayashi S, Igichi F, Kita T, Tamura T, Ito J.
    • Journal Title

      Hear Res 205・1-2

      Pages: 201-209

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nuclear translocation of beta-catenin in developing auditory epithelia of mice.2005

    • Author(s)
      Takebayashi S, Nakagawa T, Kojima K, Kim TS, Endo T, Iguchi F, Kita T, Yamamoto N, Ito J.
    • Journal Title

      Neuroreport 16・5

      Pages: 431-434

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Potential of embryonic stem cell-derived neurons for synapse formation with auditory hair cells.

    • Author(s)
      Matsumoto M, Nakagawa T, Kojima K, Sakamoto T, Ito J.
    • Journal Title

      J Neurosci Res (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea.

    • Author(s)
      Okano T, Nakagawa T, Kita T, Kada S, Yoshimoto M, Nakahata T, Ito J.
    • Journal Title

      J Neurosci Res (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Potential of embryonic stem cell-derived neurons for synapse formation with auditory hair cells

    • Author(s)
      Matsumoto, M., Nakagawa, T., Kojima, K., Sakamoto
    • Journal Title

      J Neurosci Res. (in-print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone marrow-derived cells expressing Mal are constitutively present as resident tissue macrophages in the mouse cochlea

    • Author(s)
      Okano, T., Nakagawa, T., Kita, T., Rada, S., Yoshimoto, M., Nakahata, T
    • Journal Title

      J Neurosci Res. (in-print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Future stem cell therapy for age-related hearing impairment.2007

    • Author(s)
      Nakagawa T
    • Organizer
      Age Related Hearing Impairment Congress
    • Place of Presentation
      Antwerp, Belgium
    • Year and Date
      2007-05-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Future stem cell therapy for age-related hearing impairment2007

    • Author(s)
      Nakagawa, T
    • Organizer
      Age Related Hearing Impairment Congress, Antwerp, Belgium
    • Year and Date
      2007-05-25
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 胚性幹細胞由来神経細胞移植による聴神経再生2007

    • Author(s)
      中川隆之、Lee Kyu Yup、岡野高之、松本昌宏、嘉田真平、扇田秀章、堀 龍介、小島 憲、坂本達則、平海晴一、藤本康子、伊藤壽一
    • Organizer
      第10回日本組織工学会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 胚性幹細胞由来神経細胞移植による聴覚再生2007

    • Author(s)
      中川隆之、Lee Kyu Yup、岡野高之、松本昌宏、嘉田真平、扇田秀章、堀 龍介、小島 憲、坂本達則、平海晴一、藤本康子、伊藤壽一
    • Organizer
      第28回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 内リンパ嚢および前庭感覚上皮における骨髄由来細胞の分布2007

    • Author(s)
      中川隆之、岡野高之、伊藤壽一
    • Organizer
      第66回日本めまい平衡医学会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 微細ガラス管を用いた蝸牛軸への細胞移植について2007

    • Author(s)
      扇田秀章、中川隆之、伊藤壽一
    • Organizer
      第108回日本耳鼻咽喉科学会
    • Place of Presentation
      金沢
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 成体マウス前庭における骨髄由来細胞の免疫組織学的解析2007

    • Author(s)
      岡野高之、中川隆之、嘉田真平、扇田秀章、伊藤壽一
    • Organizer
      第108回日本耳鼻咽喉科学会
    • Place of Presentation
      金沢
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 胚性幹細胞由来神経と蝸牛有毛細胞とのシナプス形成2007

    • Author(s)
      松本昌宏、中川隆之、小島 憲、坂本達則、伊藤壽一
    • Organizer
      第17回日本耳科学会
    • Place of Presentation
      福岡
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 微細ガラス管を用いた蝸牛軸へのES由来神経細胞の移植について2007

    • Author(s)
      扇田秀章、岡野高之、中川隆之、伊藤壽一
    • Organizer
      第17回日本耳科学会
    • Place of Presentation
      福岡
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] カニクイザル高度難聴モデルにおけるES細胞由来神経細胞移植による電気刺激聴性脳幹反応閾値の変化2007

    • Author(s)
      嘉田真平、中川隆之、藤本康子、松本昌宏、扇田秀章、堀 龍介、伊藤壽一
    • Organizer
      第17回日本耳科学会
    • Place of Presentation
      福岡
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Local delivery of IGF1 by gelatin hydrogels for hearing loss2007

    • Author(s)
      Nakagawa T, Okano T, Lee KY, Ito J, et. al.
    • Organizer
      2007 American Academy of Otolaryngology-Head and Neck Surgery Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Characterization and Mobilization of Cochlear Microglia/macrophages2007

    • Author(s)
      Nakagawa T, Okano T, Ito J.
    • Organizer
      2007 American Academy of Otolaryngology-Head and Neck Surgery Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Therapeutic effect of IGF-1-Hydrogel therapy on noise-induced hearing loss in guinea pigs2007

    • Author(s)
      Nakagawa T, Lee KY, Ono K, Okano T, Matsumoto M, Hiraumi H, Tabata Y, Lee SH, Ito J.
    • Organizer
      The 30th Midwinter Meeting of Association for Research in Otolaryngology
    • Place of Presentation
      Denver, Colorado, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Dynamic mobilization of microglia/microphage in the mouse inner ear2007

    • Author(s)
      Okano T, Nakagawa T, Kita T, Kada S, Ito J
    • Organizer
      The 30th Midwinter Meeting of Association for Research in Otolarvngology
    • Place of Presentation
      Denver, Colorado, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ito J2007

    • Author(s)
      Nakagawa, T., Okano, T., Lee, K., Y
    • Organizer
      Local delivery of IGF1 by gelatin hydrogels for hearing loss. 2007 American Academy of Otolaryngology-Head and Neck Surgery Annual Meeting, Washington DC
    • Place of Presentation
      USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ito J2007

    • Author(s)
      Nakagawa, T., Okano, T
    • Organizer
      Characterization and Mobilization of Cochlear Microglia/macrophages. 2007 American Academy of Otolaryngology- Head and Neck Surgery Annual Meeting, Washington DC
    • Place of Presentation
      USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ito J2007

    • Author(s)
      Nakagawa, T., Lee, KY, Ono, K., Okano, T., Matsumoto, M., Hiraumi, H., Tabata, Y., Lee, SH
    • Organizer
      Therapeutic effect of IGF-1-Hydrogel therapy on noise-induced hearing loss in guinea pigs. The 30th Midwinter Meeting of Association for Research in Otolaryngology(Denver, Colorado)
    • Place of Presentation
      USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ito J2007

    • Author(s)
      Okano, T., Nakagawa, T., Kita, T., Kada, S
    • Organizer
      Dynamic mobilization of microglia/microphage in the mouse inner ear. The 30th Midwinter Meeting of Association for Research in Otolaryngology(Denver, Colorado)
    • Place of Presentation
      USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 胚性幹細胞由来神経細胞移植による聴神経再生2007

    • Author(s)
      中川隆之、Lee Kyu Yup、岡野高之、松本昌宏、嘉田真平、扇田秀章、堀 龍介、小島 憲、坂本達則、平海晴一、藤本康子、伊藤壽一
    • Organizer
      第10回日本組織工学会.
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] Local delivery of IGFl by gelatin hydrogels for hearingloss.2007

    • Author(s)
      Nakagawa T, Okano T, Lee KY, Ito J.
    • Organizer
      2007 American Academy of Otolaryngology- Head and Neck Surgery Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Characterization and Mobilization of Cochlear Microglia/macrophages.2007

    • Author(s)
      Nakagawa T, Okano T, Ito J.
    • Organizer
      2007 American Academy of Otolaryngology- Head and Neck Surgery Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2007 Annual Research Report
  • [Book] メディカルバイオ2008

    • Author(s)
      中川隆之
    • Total Pages
      6
    • Publisher
      オーム社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 実験医学2007

    • Author(s)
      中川隆之、吉川弥生、伊藤壽一
    • Total Pages
      6
    • Publisher
      実験医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] ここまで進んだ幹細胞研究と再生医療20062006

    • Author(s)
      中川隆之, 伊藤壽一
    • Total Pages
      207
    • Publisher
      体性幹細胞による内耳再生
    • Related Report
      2006 Annual Research Report
  • [Book] 細胞増殖因子と再生医療2006

    • Author(s)
      中川隆之, 伊藤壽一
    • Publisher
      内耳
    • Related Report
      2006 Annual Research Report
  • [Book] A New Method for Drug application to the Inner Ear. In : Menier's Disease Recent Research Supported by the Japanese Ministry of Health, Labor and Welfare, ORL (Guset Editor Takahashi.)2005

    • Author(s)
      Ito J, Endo T, Nakagawa T, Kita T, Kim TS, Iguchi F.
    • Total Pages
      310
    • Publisher
      kargar
    • Related Report
      2005 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~ent/

    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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