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Generation of human iPS cells derived from ocular tissues and their use for functional analysis, novel diagnostic technique and medical treatment

Research Project

Project/Area Number 24659770
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

AZUMA Noriyuki  独立行政法人国立成育医療研究センター, その他部局等, その他 (10159395)

Co-Investigator(Kenkyū-buntansha) UMEZAWA Akihiro  国立成育医療研究センター, 再生医療センター, 副所長・再生医療センター長 (70213486)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords再生医学 / 遺伝学 / 遺伝子・細胞治療 / 角膜 / 網膜 / 遺伝子・細胞医療
Outline of Final Research Achievements

We generated primitive retinal tissues from human iPS cells, mouse iPS cells and mouse ES cells. We also generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells. After development of the optic vesicle from the induced stem cell embryoid body in three-dimensional culture, conversion to two-dimensional culture resulted in differentiation of RGCs. Axons extended radially from the margin of the clump. Induced RGCs expressed specific markers by quantitative PCR and immunohistochemistry. The long, prominent axons contained neurofilaments and tau, and manifested anterograde axonal transport and sodium-dependent action potentials. The ability to generate RGCs with functional axons uniformly and at a high rate may contribute to both basic and clinical science, including embryology, neurology, pathognomy, and treatment of various optic nerve diseases that threaten vision

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (40 results)

All 2015 2014 2013 2012 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results,  Acknowledgement Compliant: 8 results,  Open Access: 5 results) Presentation (16 results) (of which Invited: 6 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells.2015

    • Author(s)
      Tanaka T, Yokoi T, Tamalu F, Watanabe S, Nishina S, Azuma N.
    • Journal Title

      Sci. Rep.

      Volume: 10

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Generation of pluripotent stem cells without the use of genetic material.2015

    • Author(s)
      Higuchi A, Ling QD, Kumar SS, Munusamy MA, Alarfaj AA, Chang Y, Kao SH, Lin KC, Wang HC, Umezawa A.
    • Journal Title

      Lab Invest

      Volume: 95(1) Pages: 26-42

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A practical guide to induced pluripotent stem cell research using patient samples.2015

    • Author(s)
      Santostefano KE, Hamazaki T, Biel NM, Jin S, Umezawa A, Terada N
    • Journal Title

      Lab Invest

      Volume: 95(1) Pages: 4-13

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD.2014

    • Author(s)
      1Seko Y, Azuma N, Ishii T, Komuta Y, Miyamoto K, Miyagawa Y, Kaneda M, Umezawa A.
    • Journal Title

      Genes Cells.

      Volume: 19 Pages: 198-208

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Three Cases of rhegmatogenous retinal detachment associated with regressed retinoblastoma after conservative tumor therapy.2014

    • Author(s)
      Tanaka M, Yokoi T, Kobayashi Y, Nishina S, Noda E, Ito M, Azuma N.
    • Journal Title

      Retin Cases Brief Rep.

      Volume: 8 Pages: 223-226

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Surgical outcomes of progressive tractional retinal detachment associated with familial exudative vitreoretinopathy.2014

    • Author(s)
      Yamane T, Yokoi T, Nakayama Y, Nishina S, Azuma N.
    • Journal Title

      Am J Ophthalmol 2

      Volume: 158 Pages: 1049-1055

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability2014

    • Author(s)
      Fukawatase Y, Toyoda M, Okamura K, Nakamura K, Nakabayashi K, Takada S, Yamazaki-Inoue M, Masuda A, Nasu M, Hata K, Hanaoka K, Higuchi A, Takubo K, Umezawa A
    • Journal Title

      Sci Rep

      Volume: 4:5421 Pages: 5421-5421

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD.2014

    • Author(s)
      Seko Y, Azuma N, Ishii T, Komuta Y, Miyamoto K, Miyagawa Y, Kaneda M, Umezawa A.
    • Journal Title

      Genes Cells

      Volume: 19(3) Pages: 198-208

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Three cases of rhegmatogenous retinal detachment associated with regressed retinoblastoma after conservative therapy.2014

    • Author(s)
      Tanaka M, Yokoi T, Ito M, Kobayashi Y, Noda E, Matsuoka K, Nishina S, Azuma N.
    • Journal Title

      Retin Cases Brief Rep Epub

      Volume: In Press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD2014

    • Author(s)
      Seko Y, Azuma N, Ishii T, Komuta Y, Miyamoto K, Miyagawa Y, Kaneda M, Umezawa A
    • Journal Title

      Gene to Cells Epub

      Volume: 19(3) Issue: 3 Pages: 198-208

    • DOI

      10.1111/gtc.12127

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a premacular vitreous pocket.2013

    • Author(s)
      Yokoi T, Toriyama N, Yamane T, Nakayama Y, Nishina S, Azuma N
    • Journal Title

      JAMA Ophthalmol.

      Volume: 131(8) Pages: 1095-1096

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Electroretinography combined with spectral domain optical coherence tomography to detect retinal damage in shaken baby syndrome.2013

    • Author(s)
      Nakayama Y, Yokoi T, Nishina S, Okuyama M, Azuma N
    • Journal Title

      J AAPOS

      Volume: 17(4) Pages: 411-413

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Visual outcomes after early vitreous surgery for aggressive posterior retinopathy of prematurity2013

    • Author(s)
      Azuma N, Ito M, Yokoi T, Nakayama Y, Nishina S.
    • Journal Title

      JAMA Ophthalmol

      Volume: 131(10) Pages: 1309-1313

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 未熟児網膜症治療の現状2013

    • Author(s)
      東 範行
    • Journal Title

      日眼会誌

      Volume: 117(8) Pages: 605-607

    • NAID

      10031189432

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 太陽電池を用いた人工視覚2013

    • Author(s)
      東 範行
    • Journal Title

      日本の眼科

      Volume: 84 Pages: 1550-1553

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of functioning human corneal endothelial cell line with high growth potential.2012

    • Author(s)
      Yokoi T, Seko Y, Yokoi T, Makino H, Hatou S, Yamada M, Kiyono T, Umezawa A, Nishina H, Azuma N.
    • Journal Title

      PLoS One

      Volume: 7(1) Issue: 1 Pages: e29677-e29677

    • DOI

      10.1371/journal.pone.0029677

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Derivation of Human Differential Photoreceptor-like Cells from the Iris by Defined Combinations of CRX, RX and NEUROD.2012

    • Author(s)
      Seko Y, Azuma N, Kaneda M, Nakatani K, Miyagawa Y, Noshiro Y, Kurokawa R, Okano H, Umezawa A.
    • Journal Title

      PLoS One

      Volume: 7(4) Issue: 4 Pages: e35611-e35611

    • DOI

      10.1371/journal.pone.0035611

    • NAID

      120007137243

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Two Novel Mutations in the EYS Gene Are Possible Major Causes of Autosomal Recessive Retinitis Pigmentosa in the Japanese Population.2012

    • Author(s)
      Nakanishi H, Ueno S, Yokoi T, Hikoya A, Fujita T, Zhao Y, Nishina S, Shin JP, Kim IT, Yamamoto S, Azuma N, Terasaki H, Sato M, Kondo M, Minoshima M, Hotta Y.
    • Journal Title

      PLoS One

      Volume: 7(2) Issue: 2 Pages: e31036-e31036

    • DOI

      10.1371/journal.pone.0031036

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features of congenital retinal folds.2012

    • Author(s)
      Nishina S、Suzuki Y, Yokoi T, Kobayashi Y, Noda E, Azuma N.
    • Journal Title

      Am J Ophthalmol

      Volume: 153(1) Issue: 1 Pages: 81-87

    • DOI

      10.1016/j.ajo.2011.06.002

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Survey of microphthalmia in Japan.2012

    • Author(s)
      Nishina S, Kurosaka D, Nishida Y, Kondo H, Kobayashi Y, Azuma N.
    • Journal Title

      Jpn J Ophthalmol

      Volume: 56 Issue: 3 Pages: 198-202

    • DOI

      10.1007/s10384-012-0126-7

    • NAID

      10030626740

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ophthalmic features of CHARGE syndrome with CHD7 mutations. 158A(3) : 514-82012

    • Author(s)
      Nishina S, Kosaki R, Yagihashi T, Azuma N, Okamoto N, Hatsukawa Y, Kurosawa K, Yamane T, Mizuno S, Tsuzuki K, Kosaki K
    • Journal Title

      American Journal of Medical Genetics

      Volume: 158 Issue: 3 Pages: 514-518

    • DOI

      10.1002/ajmg.a.34400

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features of anterior segment dysgenesis associated with congenital corneal opacities2012

    • Author(s)
      Shigeyasu C, Yamada M, Mizuno Y, Yokoi T, Nishina S, Azuma N
    • Journal Title

      Cornea

      Volume: 31 Issue: 3 Pages: 293-298

    • DOI

      10.1097/ico.0b013e31820cd2ab

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 小児の眼底が教えてくれること -疾患の理解から未来の医療へ-.2014

    • Author(s)
      東 範行
    • Organizer
      第68回日本臨床眼科学会
    • Place of Presentation
      神戸
    • Year and Date
      2014-11-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of retinal structure and function in eyes with optic nerve hypoplasia. An International Perspective of Pediatric Ophthalmology & Strabismus2013

    • Author(s)
      Nishina S, Yokoi T, Nakayama Y, Ui M, Tanaka M, Azuma N
    • Organizer
      AAPOS&SNEC joint meeting
    • Place of Presentation
      Singapore
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of a premacular vitreous pocket2013

    • Author(s)
      Yokoi T, Toriyama N, Yamane T, Nakayama Y, Nishina S, Azuma N
    • Organizer
      ARVO
    • Place of Presentation
      Seattle
    • Related Report
      2013 Research-status Report
  • [Presentation] Surgical outcomes of traction retinal detachment associated with familial exudative vitreoretinopathy2013

    • Author(s)
      Azuma N.
    • Organizer
      AAPOS&SNEC joint meeting
    • Place of Presentation
      Singapore
    • Related Report
      2013 Research-status Report
  • [Presentation] Structure and function of the fovea region in eyes with peripapillary staphyloma.2013

    • Author(s)
      Nakayama Y, Tanaka M, Yokoi T, Nishina S. Azuma N.
    • Organizer
      The 8th APVRS Congress
    • Place of Presentation
      Nagoya
    • Related Report
      2013 Research-status Report
  • [Presentation] Detailed structure of optic disc pits examined by swept-source OCT.2013

    • Author(s)
      Yokoi T, Nakayama Y, Nishina S. Azuma N
    • Organizer
      The 8th APVRS Congress
    • Place of Presentation
      Nagoya
    • Related Report
      2013 Research-status Report
  • [Presentation] 眼の発生と進化 ーさまざまな動物の眼やヒトの進化からー2012

    • Author(s)
      東 範行
    • Organizer
      Retina-Glaucoma Meeting
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 視神経の構造と機能2012

    • Author(s)
      東 範行
    • Organizer
      Japan Macula Club
    • Place of Presentation
      蒲郡
    • Related Report
      2012 Research-status Report
  • [Presentation] Survey of mucrophthalmos in Japan2012

    • Author(s)
      Nishina S, Yokoi N,
    • Organizer
      American Academy of Ophthalmology
    • Place of Presentation
      Chicago
    • Related Report
      2012 Research-status Report
  • [Presentation] Structure and function of optic nerve hypoplasia.2012

    • Author(s)
      Nishia S, Nakayama Y, Yokoi T, Yamane T, Azuma N.
    • Organizer
      第51回網膜硝子体学会
    • Place of Presentation
      甲府
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Structure and function of the fovea region in eyes with peripapillary staphyloma.

    • Author(s)
      Nakayama Y, Tanaka M, Yokoi T, Nishina S, Azuma N.
    • Organizer
      AAPOS&SNEC joint meeting
    • Place of Presentation
      Singapore
    • Related Report
      2013 Research-status Report
  • [Presentation] SS-OCTによる小児の眼底疾患所見―Pit-macular症候群の発生機序―

    • Author(s)
      横井 匡,東 範行
    • Organizer
      Japan Macula Club
    • Place of Presentation
      蒲郡
    • Related Report
      2013 Research-status Report
  • [Presentation] 小児眼疾患の診かた考え方

    • Author(s)
      東 範行
    • Organizer
      さざなみ眼科研究会
    • Place of Presentation
      滋賀
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 小児の内眼手術

    • Author(s)
      東 範行
    • Organizer
      大阪眼科手術シンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 未熟児網膜症の診断と治療

    • Author(s)
      東 範行
    • Organizer
      千葉県眼科手術懇話会
    • Place of Presentation
      幕張
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 小児の眼底疾患

    • Author(s)
      東 範行
    • Organizer
      東京都眼科医会卒後研修会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 新体系看護学全書 小児看護学2 健康障害をもつ小児の看護. 眼疾患2013

    • Author(s)
      野田英一郎, 東 範行
    • Total Pages
      642
    • Publisher
      メヂカルフレンド社
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 網膜神経節細胞の作製方法2014

    • Inventor(s)
      東 範行
    • Industrial Property Rights Holder
      東 範行
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-08-08
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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