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Regenerative therapy using gene-edited iPS cells derived from an epidermolysis bullosa patient

Research Project

Project/Area Number 17H05089
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionNiigata University

Principal Investigator

Shinkuma Satoru  新潟大学, 医歯学系, 准教授 (00613788)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords表皮水疱症 / reframing治療 / 遺伝子治療 / iPS細胞 / 遺伝子編集 / フレームシフト変異 / 再生医療 / CRISPR/Cas9 / 皮膚科学
Outline of Final Research Achievements

Recessive dystrophic epidermolysis bullosa is an inherited disorder characterized by blisters and erosions on the whole body. It was considered that a radical treatment could be developed by combining a local treatment in which fibroblasts and epidermal keratinocytes differentiated from iPS cells genetically treated using gene editing technology such as CRISPR/Cas9 are directly administered to the affected area and a systemic treatment by systemic administration of hematopoietic/mesenchymal stem cells. In this study, we established iPS cells from epidermal keratinocytes derived from patients with epidermolysis bullosa, and confirmed the possibility of differentiation into mesenchymal stem cells. Furthermore, we have established a technology to specifically and efficiently repair gene mutations that are frequently found in Japanese patients.

Academic Significance and Societal Importance of the Research Achievements

生体において免疫は他人の細胞を排除するように働くため、再生医療には自己の細胞を用いる必要がある。遺伝性疾患では、患者細胞には遺伝子変異があるため、患者の細胞に遺伝子治療を施して、再度患者自身に戻す必要がある。この治療法を実用化するためには、①細胞を必要分増殖させること、また②遺伝子治療した細胞を全身に行き渡らせる必要があった。本研究では、患者由来細胞の遺伝子治療法を確立し、さらに自己増殖が可能なiPS細胞を皮膚細胞や全身に遊走することができる細胞に分化させることに成功し、遺伝性皮膚疾患の遺伝子・再生医療に向けた実証実験を行った。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Functional analysis of keratin filament network formation indicates clinical severity of epidermolysis bullosa simplex.2020

    • Author(s)
      Ansai O, Shinkuma S, Hayashi R, Tomii K, Deguchi T, Aizawa A, Fujiwara H, Shimomura Y, Abe R.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: i n press Issue: 10

    • DOI

      10.1111/jdv.16495

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amino acid charge and epidermolysis bullosa simplex severity: genotype‐phenotype correlations2019

    • Author(s)
      Ansai O.、Shinkuma S.、Kabata Y.、Katsumi T.、Hagiwara R.、Tomii K.、Fujikawa H.、Matsubara M.、Abe R.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 34 Issue: 2

    • DOI

      10.1111/jdv.15990

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electron Microscopic and Immunohistochemical Findings of the Epidermal Basement Membrane in Two Families with Nail-patella Syndrome2019

    • Author(s)
      Shinkuma S、Nakamura H、Maehara M、Takashima S、Nomura T、Fujita Y、Hasegawa S、Sato-Matsumura K、Abe R、Shimizu H
    • Journal Title

      Acta Dermato Venereologica

      Volume: 99(12) Pages: 1110-1115

    • DOI

      10.2340/00015555-3318

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient gene reframing therapy for recessive dystrophic epidermolysis bullosa using CRISPR/Cas92019

    • Author(s)
      Takashima Shota、Shinkuma Satoru、Fujita Yasuyuki、Nomura Toshifumi、Ujiie Hideyuki、Natsuga Ken、Iwata Hiroaki、Nakamura Hideki、Vorobyev Artem、Abe Riichiro、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: in press Issue: 8 Pages: 1711-1721

    • DOI

      10.1016/j.jid.2019.02.015

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel COL7A1 mutation in a family with bullous dermolysis of the newborn: Phenotypic variability associated with a COL7A1 mutation within the same family2018

    • Author(s)
      Takashima Shota、Shinkuma Satoru、Fujita Yasuyuki、Natsuga Ken、Nomura Toshifumi、Hida Tokimasa、Ishikawa Shuku、Nakamura Hideki、Abe Riichiro、Shimizu Hiroshi
    • Journal Title

      The Journal of Dermatology

      Volume: 印刷中 Issue: 9

    • DOI

      10.1111/1346-8138.14287

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The development of induced pluripotent stem cell-derived mesenchymal stem/stromal cells from normal human and RDEB epidermal keratinocytes2018

    • Author(s)
      Nakayama Chihiro、Fujita Yasuyuki、Matsumura Wakana、Ujiie Inkin、Takashima Shota、Shinkuma Satoru、Nomura Toshifumi、Abe Riichiro、Shimizu Hiroshi
    • Journal Title

      Journal of Dermatological Science

      Volume: 91 Issue: 3 Pages: 301-310

    • DOI

      10.1016/j.jdermsci.2018.06.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita2018

    • Author(s)
      Watanabe Mika、Natsuga Ken、Shinkuma Satoru、Shimizu Hiroshi
    • Journal Title

      The Journal of Dermatology

      Volume: 45 Issue: 5 Pages: 515-521

    • DOI

      10.1111/1346-8138.14222

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [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] Frameshift mutations in different exons of Col17a1 lead to distinctive phenotype of junctional epidermolysis bullosa model mice2019

    • Author(s)
      Hong Ha Nguyen, Satoru Shinkuma, Osamu Ansai, Yudai Kabata, Shota Takashima, Masashi Mori, Masahito Ikawa, Hiroshi Shimizu, Riichiro Abe
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exploring the possibilities of genome editing therapy for dystrophic epidermolysis bullosa via non-homologous end-joining pathway2019

    • Author(s)
      Satoru Shinkuma
    • Organizer
      The 4th Annual Meeting of Chinese Society for Investigative Dermatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Efficient reframed gene therapy for recessive dystrophic epidermolysis bullosa using CRISPR/Cas9.2018

    • Author(s)
      Shota Takashima, Satoru Shinkuma, Yasuyuki Fujita, Toshifumi Nomura, Hideki Nakamura, Hiroshi Shimizu
    • Organizer
      The 7th International Investigative Dermatology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The development of mesenchymal stem/stromal cells from 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] Gene-edition targeting mutation site recovers null-expression of type VII collagen caused by frameshift mutation via non-homologous end joining in Recessive Dystrophic Epidermolysis Bullosa2017

    • Author(s)
      S Takashima, S Shinkuma, Y Fujita, T Nomura, H Ujiie, R Abe, H Shimizu
    • Organizer
      the 76th annual meeting of society for investigative dermatology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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