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Treatment of epidermolysis bullosa with revertant keratinocyte-derived iPS cells

Research Project

Project/Area Number 15K09753
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionHokkaido University

Principal Investigator

Fujita Yasuyuki  北海道大学, 大学病院, 講師 (80374437)

Co-Investigator(Kenkyū-buntansha) 清水 宏  北海道大学, 医学研究院, 教授 (00146672)
乃村 俊史  北海道大学, 大学病院, 講師 (50399911)
夏賀 健  北海道大学, 大学病院, 講師 (70645457)
Research Collaborator MATSUMURA WAKANA  北海道大学, 大学院医学院, 大学院生
NAKAYAMA CHIHIRO  北海道大学, 大学院医学院, 大学院生
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords表皮水疱症
Outline of Final Research Achievements

Cell-based therapies such as allogeneic mesenchymal stem/stromal cells (MSCs) transplantation for recessive dystrophic epidermolysis bullosa (RDEB) were explored. However, some hurdles exist to come over in current MSC-based therapies; limited proliferation and limited cell survival. To solve these problems, we focused on keratinocyte-derived induced pluripotent stem cells (iPSCs). Keratinocytes from intact areas of patients might have revertant mosaicism where the pathogenic mutations are spontaneously corrected. In this study, we succeeded to develop MSCs from keratinocytes-derived iPSCs (KC-iPSC-MSCs) of normal human and a RDEB patient. Keratinocytes-derived iPSCs (KC-iPSCs) were cultured with activin A, BIO and BMP4 to induct mesoderm lineage, and then cultured with bFGF and EGF. In 14 days, spindle-shaped cells
appeared which showed mesenchymal differentiation. Furthermore, the intravenous injection of the KC-iPSC-MSCs into wounded mice induced human type VII collagen.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016 2015

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results)

  • [Journal Article] Establishment of integration-free induced pluripotent stem cells from human recessive dystrophic epidermolysis bullosa keratinocytes2018

    • Author(s)
      Matsumura Wakana、Fujita Yasuyuki、Nakayama Chihiro、Shinkuma Satoru、Suzuki Shotaro、Nomura Toshifumi、Abe Riichiro、Shimizu Hiroshi
    • Journal Title

      Journal of Dermatological Science

      Volume: 89 Issue: 3 Pages: 263-271

    • DOI

      10.1016/j.jdermsci.2017.11.017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The development of mesenchymal stem/stromal cellsfrom keratinocyte-derived induced pluripotent stem cells (iPSCs).2017

    • Author(s)
      Chihiro Nakayama, Yasuyuki Fujita, Wakana Matsumura, Shota Takashima, Satoru Shinkuma, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical management and experimental findings in epidermolysis bullosa.2016

    • Author(s)
      Yasuyuki Fujita, Hiroshi Shimizu
    • Organizer
      Asia-Pacific Combined Dermatology Research 2016 Conference
    • Place of Presentation
      Noosa, Australia
    • Year and Date
      2016-08-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Emerging cell therapies for epidermolysis bullosa.2016

    • Author(s)
      Yasuyuki Fujita
    • Organizer
      Asia-Pacific Conbined Dermatology Research Conference
    • Place of Presentation
      Sheraton Hotel (Noosa, Australia)
    • Year and Date
      2016-08-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of transgene-free induced pluripotent stem cells from keratinocytes of recessive dystrophic epidermolysis bullosa patients.2015

    • Author(s)
      Wakana Matsumura, Yasuyuki Fujita, Satoru Shinkuma, Inkin Ujiie, Takuma Matsumoto, Toshifumi Nomura, Riichiro Abe, Hiroshi Shimizu
    • Organizer
      The 40th Annual Meeting of the Japanese Society for Investigative Dermatology.
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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