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2009 Fiscal Year Final Research Report

Gene therapy, cellular transplantation and reproducing medicine for corneal diseases

Research Project

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Project/Area Number 18390473
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

AZUMA Noriyuki  National Research Institute for Child Health and Development, 眼科, 医長 (10159395)

Co-Investigator(Kenkyū-buntansha) NISHINA Sachiko  国立成育医療センター(研究所), 眼科, 医員 (40237954)
YOKOI Tadashi  国立成育医療センター(研究所), 眼科, レジデント (80514025)
UMEZAWA Akihiro  国立成育医療センター(研究所), 生殖・細胞医療研究部, 部長 (70213486)
HATA Jyunichi  国立成育医療センター(研究所), 名誉総長 (90051614)
ISHIKAWA Kaoru  NTT北関東病院, 眼科, 非常勤 (10338121)
OKUYAMA Torayuki  国立成育医療センター(研究所), 生殖・細胞医療研究部, 共同研究員 (40177192)
Project Period (FY) 2006 – 2009
Keywords角膜 / 遺伝子治療 / 細胞移植 / 再生医学 / 幹細胞 / 遺伝学
Research Abstract

We investigated about gene therapy, cellular transplantation, reproducing medicine for corneal diseases. By lamellar keratotomy, gene induction and cellular transplantation were effectively performed into the cornea. By introducing β-glucronidase gene or transplantation of bone marrow stem cell using this method, corneal opacity in the type VII mucopolysaccharidosis model mouse was successfully treated. The method may be applied for treatment of human corneal diseases. We identified novel Pax6 mutations in a variety of human anterior segment eye anomalies. Pluripotential stem cells were isolated from the infantile corneal tissues obtained by enucleation surgery, and cultured and profiled by gene tips. The corneal epithelia were continuously-cultivated, or strained by induction of immortal genes. In these culture cells, expression of proteins specific for the corneal epithelium was identified by immunohistochemistry and RTPCR study. Na-K ATPase dependent pumping function also was detected by Ussing chamber technique. These corneal cells may be useful for reproducing human cornea and transplantation of corneal epithelia.

  • Research Products

    (72 results)

All 2010 2009 2008 2007 2006 Other

All Journal Article (57 results) Presentation (8 results) Book (5 results) Remarks (2 results)

  • [Journal Article] Heterozygous OTX2 mutations are associated with variable pituitary phenotype.2010

    • Author(s)
      Dateki S, Kosaka K, Hasegawa K, Tanaka H, Azuma N, Yokoya S, Muroya K, Adachi M, Tajima T, Motomura K, Kinoshita E, Moriuchi H, Fukami M, Ogata T
    • Journal Title

      J Clin Endocrinol Metab 95

      Pages: 756-764

  • [Journal Article] Risk Factors for Recurrent Fibrovascular Proliferation in Aggressive Posterior Retinopathy of Prematurity after Early Vitreous Surgery.2010

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

      Am J. Ophthalmol (in press)

  • [Journal Article] p38 mitogen-activated protein kinase controls a switch between cardiomyocyte and neuronal commitment of murine embryonic stem cells by activating MEF2C-dependent BMP2 transcription2010

    • Author(s)
      Wu J, Kubota J, Hirayama J, Nagai Y, Nishina S, Yokoi T, Asaoka Y, Seo J, Shimizu N, Kajiho H, Watanabe T, Azuma N, Katada T, Nishina H
    • Journal Title

      Stem Cells Dev (in press)

  • [Journal Article] 液晶視力表システムチャートSC-2000によるロービジョン児のコントラスト視力測定と遮光レンズの効果2010

    • Author(s)
      伊藤-清水里美・仁科幸子・赤池祥子・越後貫滋子・東範行
    • Journal Title

      眼臨紀 3

      Pages: 70-73

  • [Journal Article] 国立成育医療センターにおける小児ロービジョンケアの特徴2010

    • Author(s)
      伊藤-清水里美・仁科幸子・赤池祥子・越後貫滋子・東範行
    • Journal Title

      眼臨紀 3(in press)

  • [Journal Article] 未熟児網膜症の最新の医療2010

    • Author(s)
      東範行
    • Journal Title

      医療 62(In press)

  • [Journal Article] 未熟児網膜症の診断と治療2010

    • Author(s)
      東範行
    • Journal Title

      日本眼科医会 (In press)

  • [Journal Article] Hypovascular glial overgrowth from the optic nerve head in fetuses of 16 weeks gestation.2009

    • Author(s)
      Azuma N, Hida T, Kohsaka S
    • Journal Title

      Acta Ophthalmol Scand 87(3)

      Pages: 355-357

  • [Journal Article] Ocular manifestations and prognosis of shaken baby syndrome in two Japanese children's hospitals.2009

    • Author(s)
      Kobayashi Y, Yamada K, Ohba S, Nishina S, Okuyama M, Azuma N
    • Journal Title

      Jpn J Ophthalmol 53

      Pages: 384-388

  • [Journal Article] Evaluation of scleral buckling for stage 4A retinopathy of prematurity by fluorescein angiography.2009

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

      Am J Ophthalmol 148

      Pages: 544-550

  • [Journal Article] Vascular abnormalities in aggressive posterior retinopathy of prematurity detected by fluorescein angiography.2009

    • Author(s)
      Yokoi T, Hiraoka M, Miyamoto M, Yokoi T, Kobayashi Y, Nishina S, Azuma N
    • Journal Title

      Ophthalmology 116

      Pages: 1377-1382

  • [Journal Article] Effect of early vitreous surgery for aggressive posterior retinopathy of prematurity detected by fluorescein angiography.2009

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

      Ophthalmology 116

      Pages: 2442-2447

  • [Journal Article] Congenital rotated macula with good vision and binocularity.2009

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

      Jpn J Ophthalmol 53

      Pages: 452-454

  • [Journal Article] Analysis of pathology in type I Stickler syndrome.2009

    • Author(s)
      Yokoi T, Nakagawa A, Matsuoka K, Koide R, Azuma N
    • Journal Title

      Graefe Arch Clin Exp Ophthalmol 247

      Pages: 715-718

  • [Journal Article] Pax6-5a promotes neuronal differentiation of murine embryonic stem cells.2009

    • Author(s)
      Shimizu N, Watanabe H, Kubota J, Wu J, Saito R, Yokoi T, Era T, Iwatsubo T, Watanabe T, Nishina S, Azuma N, Katada T, Nishina H.
    • Journal Title

      Biol Pharm Bull 32

      Pages: 999-1003

  • [Journal Article] CrxOS maintains self-renewal of murine embryonic stem cells.2009

    • Author(s)
      Saito R, Yamasaki T, Nagai Y, Wu J, Kajiho H, Yokoi T, Noda E, Nishina S, Niwa H, Azuma N, Katada T, Nishina H
    • Journal Title

      Biochem Biophys Res Commun 390

      Pages: 1129-1135

  • [Journal Article] 未熟児網膜症2009

    • Author(s)
      平岡美依奈・東範行
    • Journal Title

      Current Therapy 27

      Pages: 902-906

  • [Journal Article] 未熟児網膜症診療-最近の考え方2009

    • Author(s)
      東範行
    • Journal Title

      あたらしい眼科 26

      Pages: 433

  • [Journal Article] II型/Aggressive Posterior ROPに対する硝子体手術の適応と時期2009

    • Author(s)
      東範行
    • Journal Title

      あたらしい眼科 26

      Pages: 473-480

  • [Journal Article] Efficient reprogramming of human and mouse primary extra-embryonic cells to pluripotent stem cells.2009

    • Author(s)
      Nagata S, Toyoda M, Yamaguchi S, Hirano K, Makino H, Nishino K, Miyagawa Y, Okita H, Kiyokawa N, Nakagawa M, Yamanaka S, Akutsu H, Umezawa A, Tada T
    • Journal Title

      Genes Cells 14(12)

      Pages: 1395-1404

  • [Journal Article] Shortening of human cell life span by induction of p16ink4a through the platelet-derived growth factor receptor beta.2009

    • Author(s)
      Takahashi H, Toyoda M, Birumachi J, Horie A, Uyama T, Miyado K, Matsumoto K, Saito H, Umezawa A
    • Journal Title

      J Cell Physiol 221(2)

      Pages: 335-342

  • [Journal Article] Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS.2009

    • Author(s)
      Makino H, Toyoda M, Matsumoto K, Saito H, Nishino K, Fukawatase Y, Machida M, Akutsu H, Uyama T, Miyagawa Y, Okita H, Kiyokawa N, Fujino T, Ishikawa Y, Nakamura T, Umezawa A
    • Journal Title

      Exp Cell Res 315(16)

      Pages: 2727-2740

  • [Journal Article] Maintenance of pluripotency and self-renewal ability of mouse embryonic stem cells in the absence of tetraspanin CD9.2009

    • Author(s)
      Akutsu H, Miura T, Machida M, Birumachi JI, Hamada A, Yamada M, Sullivan S, Miyado K, Umezawa A
    • Journal Title

      Differentiation 78(2-3)

      Pages: 137-142

  • [Journal Article] EWS/ETS regulates the expression of the Dickkopf family in Ewing family tumor cells.2009

    • Author(s)
      Miyagawa Y, Okita H, Itagaki M, Toyoda M, Katagiri YU, Fujimoto J, Hata J, Umezawa A, Kiyokawa N
    • Journal Title

      PLoS One 4(2)

      Pages: e4634

  • [Journal Article] Exdative retinal detachment following cataract surgery in Hallermann-Streiff syndrome.2008

    • Author(s)
      Nishina S, Suzuki Y, Azuma N
    • Journal Title

      Graef's Arch Clin Exp Ophthalmol 246

      Pages: 453-455

  • [Journal Article] Glial extrusion from the regressed retinoblastoma after conservative treatment.2008

    • Author(s)
      Yokoi T, Nishina S, Azuma N
    • Journal Title

      Acta Ophthalmol Scand 86

      Pages: 462-464

  • [Journal Article] Case of aggressive posterior retinopathy of prematurity with atypical neovascular growth.2008

    • Author(s)
      Hiraoka M, Nishina S, Nakagawa A, Matsuoka K, Azuma N
    • Journal Title

      Jpn J Ophthalmol

      Pages: 417-419

  • [Journal Article] Exudative retinal detachment following cataract surgery in Hallermenn-Steiff syndrome.2008

    • Author(s)
      Nishina S, Suzuki Y, Azuma N
    • Journal Title

      Graefe Arch Clin Exp Ophthalmol 246

      Pages: 453-455

  • [Journal Article] Human sclera maintains common characteristics with cartilage throughout evolution.2008

    • Author(s)
      Seko Y, Azuma N, Takahashi Y, Makino H, Morito T, Muneta T, Matsumoto K, Saito H, Sekiya I, Umezawa A
    • Journal Title

      PLoS ONE 3(11)(Epub)

      Pages: e3709

  • [Journal Article] SOX10 mutation in Warrdenburg syndrome type II.2008

    • Author(s)
      Iso M, Fukami M, Horikawa R, Azuma N, Kawashiro N, Ogata T
    • Journal Title

      Am J Med Genet 146A

      Pages: 2162-2163

  • [Journal Article] 黄斑を形成する遺伝子システムと再生医療への応用2008

    • Author(s)
      東範行
    • Journal Title

      医学のあゆみ 226

      Pages: 965-972

  • [Journal Article] The fusing ability of sperm is bestowed by CD9-containing vesicles released from eggs in mice.2008

    • Author(s)
      Miyado K, Yoshida K, Yamagata K, Sakakibara K, Okabe M, Wang X, Miyamoto K, Akutsu H, Kondo T, Takahashi Y, Ban T, Ito C, Toshimori K, Nakamura A, Ito M, Miyado M, Mekada E, Umezawa A
    • Journal Title

      Proc Natl Acad Sci U S A 105(35)

      Pages: 12921-12926

  • [Journal Article] Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells.2008

    • Author(s)
      Hida N, Nishiyama N, Miyoshi S, Kira S, Segawa K, Uyama T, Mori T, Miyado K, Ikegami Y, Cui C, Kiyono T, Kyo S, Shimizu T, Okano T, Sakamoto M, Ogawa S, Umezawa A
    • Journal Title

      Stem Cells 26(7)

      Pages: 1695-1704

  • [Journal Article] Gremlin enhances the determined path to cardiomyogenesis.2008

    • Author(s)
      Kami D, Shiojima I, Makino H, Matsumoto K, Takahashi Y, Ishii R, Naito AT, Toyoda M, Saito H, Watanabe M, Komuro I, Umezawa A
    • Journal Title

      PLoS One 3(6)

      Pages: e2407

  • [Journal Article] Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells.2008

    • Author(s)
      Miyagawa Y, Okita H, Nakaijima H, Horiuchi Y, Sato B, Taguchi T, Toyoda M, Katagiri YU, Fujimoto J, Hata J, Umezawa A, Kiyokawa N
    • Journal Title

      Mol Cell Biol 28(7)

      Pages: 2125-2137

  • [Journal Article] Possible involvement of CD81 in acrosome reaction of sperm in mice.2008

    • Author(s)
      Tanigawa M, Miyamoto K, Kobayashi S, Sato M, Akutsu H, Okabe M, Mekada E, Sakakibara K, Miyado M, Umezawa A, Miyado K
    • Journal Title

      Mol Reprod Dev 75(1)

      Pages: 150-155

  • [Journal Article] Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor.2008

    • Author(s)
      Kawakita A, Sato K, Makino H, Ikegami H, Takayama S, Toyama Y, Umezawa A
    • Journal Title

      PLoS One 3(12)

      Pages: e3945

  • [Journal Article] Human sclera maintains common characteristics with cartilage throughout evolution.2008

    • Author(s)
      Seko Y, Azuma N, Takahashi Y, Makino H, Morito T, Muneta T, Matsumoto K, Saito H, Sekiya I, Umezawa A
    • Journal Title

      PLoS One 3(11)

      Pages: e3709

  • [Journal Article] Scleral window surgery and topical mitomycin C for nanophthalmic uveal effusion complicated by retinal failure.2007

    • Author(s)
      Suzuki Y, Nishina S, Azuma N
    • Journal Title

      Graef's Arch Clin Exp Ophthalmol 245

      Pages: 755-757

  • [Journal Article] Outcome of early surgery for bilateral congenital cataracts in eyes with microcornea2007

    • Author(s)
      Nishina S, Noda E, Azuma N
    • Journal Title

      Am J Ophthalmol 144

      Pages: 276-280

  • [Journal Article] 未熟児網膜症の早期手術2007

    • Author(s)
      東範行
    • Journal Title

      眼科診療プラクティスみんなの硝子体手術(文光堂)

      Pages: 199-200

  • [Journal Article] 血管成長のガイダンス2007

    • Author(s)
      東範行
    • Journal Title

      日本の眼科 78

      Pages: 599-600

  • [Journal Article] 網膜浮腫の発生機序と薬物治療2007

    • Author(s)
      東範行
    • Journal Title

      日本の眼科 78

      Pages: 163-1640

  • [Journal Article] Myogenic transdifferentiation of menstrual blood-derived cells.2007

    • Author(s)
      Toyoda M, Cui CH, Umezawa A
    • Journal Title

      Acta Myol 26(3)

      Pages: 176-178

  • [Journal Article] The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro.2007

    • Author(s)
      Nishiyama N, Miyoshi S, Hida N, Uyama T, Okamoto K, Ikegami Y, Miyado K, Segawa K, Terai M, Sakamoto M, Ogawa S, Umezawa A
    • Journal Title

      Stem Cells 25(8)

      Pages: 2017-2024

  • [Journal Article] Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.2007

    • Author(s)
      Okamoto K, Miyoshi S, Toyoda M, Hida N, Ikegami Y, Makino H, Nishiyama N, Tsuji H, Cui CH, Segawa K, Uyama T, Kami D, Miyado K, Asada H, Matsumoto K, Saito H, Yoshimura Y, Ogawa S, Aeba R, Yozu R, Umezawa A
    • Journal Title

      Exp Cell Res. 313(12)

      Pages: 2550-2562

  • [Journal Article] Ways for a mesenchymal stem cell to live on its own: maintaining an undifferentiated state ex vivo.2007

    • Author(s)
      Toyoda M, Takahashi H, Umezawa A
    • Journal Title

      Int J Hematol 86(1)

      Pages: 1-4

  • [Journal Article] Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation.2007

    • Author(s)
      Cui CH, Uyama T, Miyado K, Terai M, Kyo S, Kiyono T, Umezawa A
    • Journal Title

      Mol Biol Cell 18(5)

      Pages: 1586-1594

  • [Journal Article] Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts.2007

    • Author(s)
      Sugiki T, Uyama T, Toyoda M, Morioka H, Kume S, Miyado K, Matsumoto K, Saito H, Tsumaki N, Takahashi Y, Toyama Y, Umezawa A
    • Journal Title

      J Cell Biochem 100(5)

      Pages: 1240-1254

  • [Journal Article] Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2. 5 and GATA4 undergo the stochastic cardiomyogenic fate and behave like transient amplifying cells.2007

    • Author(s)
      Yamada Y, Sakurada K, Takeda Y, Gojo S, Umezawa A
    • Journal Title

      Exp Cell Res 313(4)

      Pages: 698-706

  • [Journal Article] Two patients with different features of congenital optic disc anomalies in the twe eyes.2006

    • Author(s)
      Suzuki Y, Kawase E, Nishina S, Azuma N
    • Journal Title

      Graefe Arch Clin Exp Ophthalmol 244

      Pages: 259-261

  • [Journal Article] Early vitreous surgery for aggressive posterior retinopathy of prematurity.2006

    • Author(s)
      Azuma N, Ishikwa K, Hama Y, Hiraoka M, Suzuki Y, Nishina S
    • Journal Title

      Am J Opthalmol 142

      Pages: 636-643

  • [Journal Article] Small eye phenotypes observed in a human tau gene transgenic rat.2006

    • Author(s)
      Goto K, Yamada M, Sugawara A, Itou T, Azuma N, Itou M
    • Journal Title

      Current Eye Reseach 31

      Pages: 107-110

  • [Journal Article] 重症未熟児網膜症に対する早期硝子体手術2006

    • Author(s)
      東範行
    • Journal Title

      日本の眼科 77

      Pages: 1113-1120

  • [Journal Article] 重症未熟児網膜症の早期硝子体手術2006

    • Author(s)
      東範行
    • Journal Title

      日眼会誌 110

      Pages: 822-829

  • [Journal Article] 重症未熟児網膜症の治療2006

    • Author(s)
      東範行
    • Journal Title

      日本小児科学会雑誌 110

      Pages: 1616-1623

  • [Journal Article] Increased mobilization of c-kit+ Sca-1+ Lin-(KSL) cells and colony-forming units in spleen (CFU-S) following de novo formation of a stem cell niche depends on dynamic, but not stable, membranous ossification.2006

    • Author(s)
      Nagayoshi K, Ohkawa H, Yorozu K, Higuchi M, Higashi S, Kubota N, Fukui H, Imai N, Gojo S, Hata J, Kobayashi Y, Umezawa A
    • Journal Title

      J Cell Physiol 208(1)

      Pages: 188-194

  • [Presentation] Role of the Pax6 gene in the formation of highly organized eye architectures.2009

    • Author(s)
      Azuma N
    • Organizer
      Retinal Degeneration and Stem Cells
    • Place of Presentation
      OIST Okinawa
    • Year and Date
      20091100
  • [Presentation] 近視発症の分子機構―ヒト強膜前後軸の網羅的遺伝子発現解析から2009

    • Author(s)
      世古裕子
    • Organizer
      第24回日本眼内レンズ屈折手術学会総会
    • Place of Presentation
      シンポジウム東京
    • Year and Date
      20090600
  • [Presentation] 網膜・神経形成におけるPax6の選択スプライスの働き2008

    • Author(s)
      東範行
    • Organizer
      第1回Retina Research Meeting
    • Place of Presentation
      東京
    • Year and Date
      20081100
  • [Presentation] ファイザー賞受賞講演眼の形態形成遺伝子2008

    • Author(s)
      東範行
    • Organizer
      第62回日本臨床眼科学会
    • Place of Presentation
      東京
    • Year and Date
      20081000
  • [Presentation] 眼の発生と先天異常2008

    • Author(s)
      東範行
    • Organizer
      第112回日本眼科学会総会
    • Place of Presentation
      生涯教育講座
    • Year and Date
      20080400
  • [Presentation] 眼の形態形成遺伝子2007

    • Author(s)
      東範行
    • Organizer
      東京大学医科学研究所セミナー
    • Place of Presentation
      東京
    • Year and Date
      20070700
  • [Presentation] 眼の形態形成遺伝子2007

    • Author(s)
      東範行
    • Organizer
      東京医科歯科大学難病治療研究所セミナー
    • Place of Presentation
      東京
    • Year and Date
      20070500
  • [Presentation] 視覚器の形態形成と再生医療2007

    • Author(s)
      東範行
    • Organizer
      医学会総会
    • Year and Date
      20070400
  • [Book] 未熟児網膜症. 視能訓練士用語解説辞典2010

    • Author(s)
      東範行
    • Publisher
      メディカル葵(In press)
  • [Book] 網膜裂孔. 視能訓練士用語解説辞典2010

    • Author(s)
      東範行
    • Publisher
      メディカル葵(In press)
  • [Book] 未熟児網膜症眼底アトラス2009

    • Author(s)
      東範行・平岡美依奈
    • Publisher
      エルゼヴィア
  • [Book] 今日の小児医療指針第14版25眼疾患-先天硝子体、網膜疾患2008

    • Author(s)
      東範行
    • Publisher
      医学書院
  • [Book] 眼疾病学(丸尾敏夫・粟屋忍視能矯正学改訂第2版増補)2008

    • Author(s)
      東範行
    • Total Pages
      125-137
    • Publisher
      金原出版
  • [Remarks] 学会開催第65回日本弱視斜視学会総会・第34回日本小児眼科学会総会合同学会東 京2008.7.4-5.

  • [Remarks] 第4回Pfizer Ophthalmic Award Japan受賞2009.11

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Published: 2011-06-18   Modified: 2016-04-21  

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