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Fetal therapy model using amniotic fluid-derived iPS cells

Research Project

Project/Area Number 15K19665
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Embryonic/Neonatal medicine
Research InstitutionJikei University School of Medicine (2017-2018)
National Center for Child Health and Development (2015-2016)

Principal Investigator

Kazuhiro Kajiwara  東京慈恵会医科大学, 医学部, 助教 (40569521)

Research Collaborator Wada Seiji  
Kawasaki Tomoyuki  
Oishi Yoshie  
Akutsu Hidenori  
Sago Haruhiko  
Okamoto Aikou  
Umezawa Akihiro  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
KeywordsiPS細胞 / 分化誘導 / ケラチノサイト / 3次元培養 / 人工皮膚 / 脊髄髄膜瘤 / レチノイン酸 / 胎児治療 / 羊水 / ラット / 3D上皮
Outline of Final Research Achievements

We focused on iPS cells to develop novel treatments for fatal fetal diseases. By using the high differentiation ability of iPS cells, amniotic fluid-derived iPS cells successfully differentiated into functional keratinocytes with keratinizing ability. Furthermore, we could generate iPS cell-derived artificial skin with multilayered epidermis by three-dimensional culture. Then, we transplanted iPS cell-derived artificial skin into fetus of myelomeningocele rat model. Two days after transplantation, we detected elongation of rat epidermis at the skin defect site. Our treatment can become an innovative treatment that are minimally invasive and can apply to growing fetus in utero. Currently, we are performing placental analysis of the rat model and found the association between retinoic acid and placental development. Based on this result, we may improve the survival period of the rat model, leading to further analysis of long-term neurological prognosis.

Academic Significance and Societal Importance of the Research Achievements

脊髄髄膜瘤は皮膚や皮下組織が欠損するため脊髄が体表に露出し神経が障害される。iPS細胞は体の様々な細胞に分化する能力を持っている。我々はこの特徴を利用して、ヒト羊水から樹立されたiPS細胞をケラチノサイトに分化誘導した。さらにiPS細胞由来ケラチノサイトから人工皮膚を作成し、脊髄髄膜瘤ラットモデルに移植した。人工皮膚移植部では、ラットの皮膚が再生してくる所見が得られた。この結果から、羊水中であってもiPS細胞由来人工皮膚を移植することで脊髄髄膜瘤が治療できる可能性が見出された。これは侵襲が少なく、胎児にとって自分の細胞であることから胎児の成長に合わせた治療が可能になる画期的な治療法である。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Autonomous trisomic rescue of Down syndrome cells2019

    • Author(s)
      Inoue Momoko、Kajiwara Kazuhiro、Yamaguchi Ayumi、Kiyono Tohru、Samura Osamu、Akutsu Hidenori、Sago Haruhiko、Okamoto Aikou、Umezawa Akihiro
    • Journal Title

      Laboratory Investigation

      Volume: Feb 13 Issue: 6 Pages: 1-12

    • DOI

      10.1038/s41374-019-0230-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fetal Therapy Model of Myelomeningocele with Three-Dimensional Skin Using Amniotic Fluid Cell-Derived Induced Pluripotent Stem Cells2017

    • Author(s)
      Kajiwara Kazuhiro、Tanemoto Tomohiro、Wada Seiji、Karibe Jurii、Ihara Norimasa、Ikemoto Yu、Kawasaki Tomoyuki、Oishi Yoshie、Samura Osamu、Okamura Kohji、Takada Shuji、Akutsu Hidenori、Sago Haruhiko、Okamoto Aikou、Umezawa Akihiro
    • Journal Title

      Stem Cell Reports

      Volume: 8 Issue: 6 Pages: 1701-1713

    • DOI

      10.1016/j.stemcr.2017.05.013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] iPS 細胞由来培養皮膚を用いた脊髄髄膜瘤の新規治療戦略2019

    • Author(s)
      梶原 一紘
    • Organizer
      第37回 周産期シンポジウム (シンポジスト)
    • Related Report
      2018 Annual Research Report
  • [Presentation] ips細胞由来培養皮膚を用いた脊髄髄膜瘤の新規胎児治療法の開発2018

    • Author(s)
      梶原 一紘
    • Organizer
      第16回 日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Retinoic acid-induced placental vascular hypoplasia with Patched-1 up-regulation in rats2018

    • Author(s)
      梶原 一紘
    • Organizer
      International Federation of Placenta Associations (oral presentation)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ips細胞由来培養皮膚を用いた脊髄髄膜瘤の新規胎児治療法の開発2018

    • Author(s)
      梶原一紘
    • Organizer
      第16回日本再生医療学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Fetal therapy model of myelomeningocele with three dimensional skin using amniotic fluid derived iPS cells2017

    • Author(s)
      Kazuhiro Kajiwara
    • Organizer
      第69回日本産婦人科学会 Fetal therapy model of m
    • Related Report
      2017 Research-status Report
  • [Presentation] 第15回胎児治療学会2017

    • Author(s)
      Kazuhiro Kajiwara
    • Organizer
      羊水細胞由来iPS細胞の胎児治療への応用
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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