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Effective induction of inner ear hair cells from mouse embryonic stem cells

Research Project

Project/Area Number 22390318
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) OUJI Yukiteru  奈良県立医科大学, 医学部, 講師 (50343421)
WANAKA Akio  奈良県立医科大学, 医学部, 教授 (90210989)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords内耳 / 再生医学 / 有毛細胞 / 幹細胞 / 耳鼻科 / 分化誘導 / 聴覚再生 / 細胞移植
Research Abstract

Hearing loss is mainly caused by loss of sensory hair cells (HCs) in the organ of Corti or cochlea. Although embryonic stem (ES) cells are a promising source for cell therapy, little is known about the efficient generation of HC-like cells from ES cells. In the present study, we developed a single-medium culture method for growing embryoid bodies (EBs), in which conditioned medium (CM) from cultures of ST2 stromal cells (ST2-CM) was used for 14-day cultures of 4-day EBs. At the end of the 14-day cultures, up to 20% of the cells in EB outgrowths expressed HC-related markers, including Math1 (also known as Atoh1), myosin6, myosin7a, calretinin, α9AchR and Brn3c (also known as Pou4f3), and also showed formation of stereocilia-like structures. Further, we found that these cells were incorporated into the developing inner ear after transplantation into chick embryos. The present inner ear HC induction method using ST2-CM (HIST2 method) is quite simple and highly efficient to obtain ES-derived HC-like cells with a relatively short cultivation time.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (18 results)

All 2013 2012 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (10 results)

  • [Journal Article] Induction of inner ear hair cell-like cells from Math1-transfected mouse ES cells2013

    • Author(s)
      Ouji Y, Ishizaka S, Nakamura-Uchiyama F, Wanaka A, Yoshikawa M
    • Journal Title

      Cell Death & Disease

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dermal papilla cells serially cultured with Wnt-10b sustain their hair follicle induction activity after transplantation into nude mice2012

    • Author(s)
      Ouji Y, Ishizaka S, Yoshikawa M
    • Journal Title

      Cell Transplant

      Volume: Vol. 21 Pages: 2313-2324

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cell conditioned medium2012

    • Author(s)
      Ouji Y, Ishizaka S, Nakamura-Uchiyama F, Yoshikawa M
    • Journal Title

      Cell Death & Disease

      Volume: Vol. 3 Pages: 314-324

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carnitine-induced senescence in glioblastoma cells2012

    • Author(s)
      Yamada S, Matsuda R, Nishimura F, Nakagawa I, Motoyama Y, Park YS, Nakamura M, Nakase H, Ouji Y, Yoshikawa M
    • Journal Title

      Exp. Ther. Med

      Volume: Vol. 4 Pages: 21-25

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carnitine-induced senescence in glioblastoma cells2012

    • Author(s)
      Yamada S, Matsuda R, Nishimura F, Nakagawa I, Motoyama Y, Park YS, Nakamura M, Nakase H, Ouji Y, Yoshikawa M.
    • Journal Title

      Exp Ther Med

      Volume: 4 Pages: 21-25

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cell conditioned medium2012

    • Author(s)
      Ouji Y, Ishizaka S, Nakamura-Uchiyama F, Yoshikawa M.
    • Journal Title

      Cell Death & Disease

      Volume: 3 Issue: 5 Pages: e314-e314

    • DOI

      10.1038/cddis.2012.56

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulated differentiation of embryonic stem cells into hepatocyte-like cells by coculture with hepatic stellate cells2011

    • Author(s)
      Nishiofuku M, Yoshikawa M, Ouji Y, Saito K, Moriya K, Ishizaka S, Nishimura F, Matsuda R, Yamada S, Fukui H
    • Journal Title

      J Biosci Bioeng

      Volume: Vol. 111 Pages: 71-77

    • NAID

      110008440353

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulated differentiation of embryonic stem cells into hepatocyte-like cells by coculture with hepatic stellate cells2011

    • Author(s)
      Nishiofuku M, Yoshikawa M, Ouji Y, Saito K, Moriya K, Ishizaka S, Nishimura F, Matsuda R, Yamada S, Fukui H.
    • Journal Title

      J Biosci Bioeng

      Volume: 111 Issue: 1 Pages: 71-77

    • DOI

      10.1016/j.jbiosc.2010.08.005

    • NAID

      110008440353

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Efficient induction of inner ear hair cell-like cells from Math1-transfected mouse ES cells2013

    • Author(s)
      Yukiteru Ouji, Shigeaki Ishizaka, Fukumi Nakamura-Uchiyama, Akio Wanaka, Masahide Yoshikawa
    • Organizer
      CiRA International Symposium 2013
    • Place of Presentation
      京都市
    • Year and Date
      2013-03-11
    • Related Report
      2012 Final Research Report
  • [Presentation] Efficient induction of inner ear hair cell-like cells from Math1-transfected mouse ES cells2013

    • Author(s)
      Yukiteru Ouji, Shigeaki Ishizaka, Fukumi Nakamura-Uchiyama, Akio Wanaka, Masahide Yoshikawa
    • Organizer
      CiRA International Symposium 2013
    • Place of Presentation
      京都大学(京都市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vitro differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cells2012

    • Author(s)
      Yukiteru Ouji, Shigeaki Ishizaka, Fukumi Nakamura-Uchiyama, Akio Wanaka, Masahide Yoshikawa
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cells2012

    • Author(s)
      Yukiteru Ouji, Masahide Yoshikawa
    • Organizer
      第11回 国際幹細胞学会(ISSCR)
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-15
    • Related Report
      2012 Final Research Report
  • [Presentation] ES 細胞から内耳有毛細胞への効率的分化誘導法の開発2012

    • Author(s)
      王寺幸輝、吉川正英
    • Organizer
      奈良脳神経ネットワーク研究会
    • Place of Presentation
      奈良
    • Year and Date
      2012-01-13
    • Related Report
      2012 Final Research Report
  • [Presentation] ES細胞から内耳有毛細胞への効率的分化誘導法の開発2012

    • Author(s)
      王寺幸輝、吉川正英
    • Organizer
      奈良脳神経ネットワーク研究会
    • Place of Presentation
      奈良県立医科大学(奈良)
    • Year and Date
      2012-01-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cells2012

    • Author(s)
      Yukiteru Ouji, Masahide Yoshikawa
    • Organizer
      第11回 国際幹細胞学会(ISSCR)
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vitro differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cells2012

    • Author(s)
      Yukiteru Ouji, Shigeaki Ishizaka, Fukumi Nakamura-Uchiyama, Akio Wanaka, Masahide Yoshikawa
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vitro differentiation of mouse embryonic stem cells into inner ear hair cell by stromal cells2010

    • Author(s)
      Ouji Y, Yoshikawa M, Ishizaka S
    • Organizer
      The 16th International Conference of the International Society of the Differentiation
    • Place of Presentation
      奈良
    • Year and Date
      2010-11-16
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] In vitro differentiation of mouse embryonic stem cells into inner ear hair cells using stromal cells2010

    • Author(s)
      Ouji Y, Yoshikawa M, Ishizaka S
    • Organizer
      43rd Annual Meeting for the Japanese Society of Developmental Biologists Jointly Sponsored by the Asia-Pacific Developmental Biology Network
    • Place of Presentation
      京都
    • Year and Date
      2010-06-21
    • Related Report
      2012 Final Research Report 2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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