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Investigation on neural and ocular surface regeneration after cultivated mucosal epithelial sheet transplantation using amniotic membrane

Research Project

Project/Area Number 18591931
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

INATOMI Tsutomu  Kyoto Prefectural University of Medicine, Ophthalmology, Professor (00305583)

Co-Investigator(Kenkyū-buntansha) KAWASAKI Satoshi  Kyoto Prefectural University of Medicine, Ophthalmology, Research Associate (60347458)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsregenerative medicine / oral mucosal epithelium / cell differentiation / neural regeneration / ocular surfac / stem cell / corneal epithelium / conjunctival epithelium
Research Abstract

Cultivated mucosal epithelial transplantation using corneal epithelial stem cells and oral mucosal epithelium dramatically improves the clinical outcome of severe ocular surface reconstruction. However, the biological mechanisms behind the cell proliferation and differentiation still remain unclear. In this study, the in vivo condition of the regenerated tissue structure composed of transplanted epithelium was investigated using in vivo laser confocal microscopy. The surviving oral mucosal epithelium showed a well-differentiated, stratified epithelial structure similar to corneal epithelium. The high density and large number of basal cells indicated the active potential for cell proliferation to maintain the ocular surface. No neural regeneration was observed in the epithelial cell layer and sub-amniotic membrane region even after an extended period of time. This evidence is consistent with the low amount of ocular surface sensation.
Oral mucosal stem- and progenitor cells expressed p75 that exhibited a high affinity with neurotrophin, indicating that surviving oral mucosal epithelium may be regulated by nerve growth factor (NGF) and neurotrophin 3 and 4. Differentiated oral mucosal epithelium on the ocular surface does not express keratin 1 and 4, keratins that are specific for keratinization, but does express keratin 3 and 13. Surviving oral mucosal epithelium does not express keratin 12 that is cornea specific or MUCSAC that is specific for goblet cells. This study concluded that surviving oral mucosal epithelium on the ocular surface is able to retain the oral mucosal epithelial lineage without transdifferentiation into ocular surface epithelium.

Report

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

    (17 results)

All 2007 2006 Other

All Journal Article (15 results) (of which Peer Reviewed: 6 results) Presentation (2 results)

  • [Journal Article] A comparison between cultivated and conventional limbal stem cell transplantation for Stevens-Johnson syndrome2007

    • Author(s)
      Ang LPK, Inatomi T, et. al.
    • Journal Title

      Am J Ophthalmol 143

      Pages: 178-180

    • 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] A new grading system for the evaluation of chronic ocular manfestations in patients with Stevens-Johnson syndrome2007

    • Author(s)
      Sotozono C, Inatomi T, et. al.
    • Journal Title

      Ophthalmology 114

      Pages: 1294-1302

    • 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] Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases2007

    • Author(s)
      Nakamura T, Inatomi T, et. al.
    • Journal Title

      Ophthalmology 114

      Pages: 1080-1088

    • 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] New grading system for the evaluation of chronic ocular , manifestations in patients with Stevens-Johnson syndrome2007

    • Author(s)
      Sotozono, C, Ang, LP, Koizumi, N, Higashihara, H, Ueta, M, Inatomi, T., Yokoi, N., Kaido, M, Dogru, M, Shimazaki, J, Tsubota, K, Yamada, M , Kinoshita, S
    • Journal Title

      Ophthalmology. 114(7)

      Pages: 1294-302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases2007

    • Author(s)
      Nakamua, T, Inatomi, Cooper, LJ, Rigby, H, FullwoodN, J, Kinoshita, S
    • Journal Title

      Ophthalmology 114(6)

      Pages: 1080-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A comparison between cultivated and conventional limbal stem cell transplantation for Stevens-Johnson syndrome2007

    • Author(s)
      Ang, LP, Sotozono, C, Koizumi, N ,Suzuld, T, Inatomi, T, Kinoshita, S
    • Journal Title

      Am J Ophthalmol 114

      Pages: 1080-1088

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A comparison between cultivated and conventional limbal stem cell transplantation for Stevens-Johnson syndrome.2007

    • Author(s)
      Ang LPK, Inatomi T, et. al.
    • Journal Title

      Am J Ophthalmol 143

      Pages: 178-180

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome.2007

    • Author(s)
      Sotozono C, Inatomi T, et. al.
    • Journal Title

      Ophthalmology 114

      Pages: 1294-1302

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithelial sheets for severe ocular surface diseases.2007

    • Author(s)
      Nakamura T, Inatomi T, et. al.
    • Journal Title

      Ophthalmology 114

      Pages: 1080-1088

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A comparison between cultivated and conventional limbal stem cell transplanation for stevens-johnson syndrome.2007

    • Author(s)
      Ang LP, Sotozono C, Koizumi N, Suzuki T, Inatomi T, Kinoshita S
    • Journal Title

      Am J Ophthalmol. 143(1)

      Pages: 178-180

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty.2006

    • Author(s)
      Inatomi T et al.
    • Journal Title

      Am J Ophthalmol, 142(5)

      Pages: 757-764

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Midterm results of ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation.2006

    • Author(s)
      Inatomi T et al.
    • Journal Title

      Am J Ophthalmol, 141(2)

      Pages: 267-275

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Novel clinical application of sterilized, freeze-dried amniotic membrane to treat patients with pterygium.2006

    • Author(s)
      Nakamura T, Inatomi T, et al.
    • Journal Title

      Acta Ophthalmol Scand, 84(3)

      Pages: 401-405

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The use of autologous serum in the development of corneal and oral epithelial equivalents in patients with Stevens Johnson syndrome.2006

    • Author(s)
      Nakamura T, Inatomi T, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 47(3)

      Pages: 909-916

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Phenotypic investigation of human eyes with transplanted autologous cultivated oral mucosal epithlical sheets for severe surface diseases.

    • Author(s)
      Nakamura T, Inatomi T, Cooper LJ, Rigby H, Fullwood NJ, Kinoshita S.
    • Journal Title

      Ophthalmology In press

    • Related Report
      2006 Annual Research Report
  • [Presentation] Clinical Outcome of the Combination of Cultivated Autologous Oral Mucosal Epithelial Transplantation and Penetrating Keratoplasty2007

    • Author(s)
      Tsutohlu Inatomi
    • Organizer
      2007 ARVO Annual Meeting
    • Place of Presentation
      Fort Lauderdale FL.USA
    • Year and Date
      2007-05-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Clinical Outcome of the Combination of Cultivated Autologous Oral Mucosal Epithelial Transplantation and Pene trating Keratoplasty2007

    • Author(s)
      Inatomi, T
    • Organizer
      2007 ARVO Annual Meeting
    • Place of Presentation
      Fort Lauderdale FL. USA
    • Year and Date
      2007-05-07
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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