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Development of a new kidney regeneration method using a drug-induced cell elimination system for iPS cell derived progenitor cells

Research Project

Project/Area Number 17K16102
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

yamanaka shuichiro  東京慈恵会医科大学, 医学部, 助教 (80775544)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腎臓再生 / 再生医療 / iPS細胞 / 前駆細胞 / 腎不全 / ネフロン / ネフロン前駆細胞 / ジフテリアトキシン / 腎臓発生
Outline of Final Research Achievements

When nephron progenitor cells (NPC) extracted from mouse fetal kidney were transplanted into the fetal kidney at the same embryonic period, it was confirmed that the transplanted NPC settled in the nephron-generating region and contributed to the renal development of the kidney. However, the existing host NPCs and donor NPCs were mixed, and the new nephrons had a mosaic structure. Therefore, in order to regenerate pure nephrons constructed same-origin cells, we developed a system that eliminated only host nephron progenitor cells by administering a drug and succeeded in regenerating 100% transplanted cell-derived nephron.

Academic Significance and Societal Importance of the Research Achievements

本研究は腎不全患者救済をめざした腎臓再生の研究である。腎臓は多機能かつ構成細胞が多いため再生が最も難しい臓器と考えられている。しかし、近年ではiPS細胞からの誘導技術が向上し、ネフロン様組織の再生が実現化するようになった。だが生体内で臓器として働くまでの再生は困難であった。本成果ではiPS細胞からも誘導可能なNPCを細胞源に、生体内で尿産生能を持った腎臓再生技術を開発した。腎代替療法としての臨床応用だけでなく、ヒトiPS細胞を用いた薬剤毒性試験や病態解析などのin vivo評価系としての応用も想定され、腎不全患者の救済に多面的に資する技術になると考える。

Report

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

    (19 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Mesangial cell regeneration from exogenous stromal progenitor by utilizing embryonic kidney2019

    • Author(s)
      Saito Yatsumu、Yamanaka Shuichiro、Fujimoto Toshinari、Tajiri Susumu、Matsumoto Naoto、Takamura Tsuyoshi、Matsumoto Kei、Yokoo Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 520 Issue: 3 Pages: 627-633

    • DOI

      10.1016/j.bbrc.2019.10.080

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo regeneration of interspecies chimeric kidneys using a nephron progenitor cell replacement system2019

    • Author(s)
      Fujimoto Toshinari、Yamanaka Shuichiro、Tajiri Susumu、Takamura Tsuyoshi、Saito Yatsumu、Matsumoto Kei、Takase Kentaro、Fukunaga Shohei、Okano Hirotaka James、Yokoo Takashi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 6965-6965

    • DOI

      10.1038/s41598-019-43482-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kidney Regeneration in Later-Stage Mouse Embryos via Transplanted Renal Progenitor Cells2019

    • Author(s)
      Yamanaka Shuichiro、Saito Yatsumu、Fujimoto Toshinari、Takamura Tsuyoshi、Tajiri Susumu、Matsumoto Kei、Yokoo Takashi
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 30 Issue: 12 Pages: 2293-2305

    • DOI

      10.1681/asn.2019020148

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regenerative potential of induced pluripotent stem cells derived from patients undergoing haemodialysis in kidney regeneration2018

    • Author(s)
      Tajiri Susumu、Yamanaka Shuichiro、Fujimoto Toshinari、Matsumoto Kei、Taguchi Atsuhiro、Nishinakamura Ryuichi、Okano Hirotaka James、Yokoo Takashi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-018-33256-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration2018

    • Author(s)
      Fukunaga Shohei、Yamanaka Shuichiro、Fujimoto Toshinari、Tajiri Susumu、Uchiyama Taketo、Matsumoto Kei、Ito Takafumi、Tanabe Kazuaki、Yokoo Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 496 Issue: 4 Pages: 1176

    • DOI

      10.1016/j.bbrc.2018.01.166

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system.2017

    • Author(s)
      Yamanaka S, Tajiri S, Fujimoto T, Matsumoto K, Fukunaga S, Kim BS, Okano HJ, Yokoo T.
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1719-1732

    • DOI

      10.1038/s41467-017-01922-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 胎仔への経子宮的細胞移植法の確立と腎欠損胎仔における腎前駆細胞からのin vivo腎臓再生2019

    • Author(s)
      山中 修一郎
    • Organizer
      第18回日本再生医療学会 (神戸)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 異種動物の胎生期腎臓を足場に 利用した腎前駆細胞からの腎臓再生2019

    • Author(s)
      山中 修一郎
    • Organizer
      第46回日本臓器保存生物医学会学術集会(郡山)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ワークショップ口演, Kidney regeneration from renal progenitor cells, borrowing embryonic kidneys from other species as a developmental niche2019

    • Author(s)
      山中 修一郎
    • Organizer
      第42回 日本分子生物学会年会(福岡)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 胎仔への経子宮的細胞移植法の確立と腎欠損胎仔における腎前駆細胞からのin vivo腎臓再生2019

    • Author(s)
      山中 修一郎 ,斉藤 弥積 ,高村 毅 ,藤本 俊成 ,田尻 進 ,松本 啓 ,横尾 隆
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Exo utero method to regenerate nephrons from nephron progenitor cells in the living fetus2018

    • Author(s)
      Shuichiro Yamanaka , Yatsumu Saitou, Toshinari Fujimoto , Susumu Tajiri, Tsuyoshi Takamura, Kei Matsumoto, Takashi Yokoo
    • Organizer
      American Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration2018

    • Author(s)
      Shohei Fukunaga a , Shuichiro Yamanaka a , Toshinari Fujimoto a , Susumu Tajiri a , Taketo Uchiyama a , Kei Matsumoto a , Takafumi Ito b , Kazuaki Tanabe b , Takashi Yokoo
    • Organizer
      55th ERA-EDTA 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腎臓再生への挑戦 ネフロン前駆細胞を用いた実質臓器再生への挑戦2018

    • Author(s)
      山中 修一郎
    • Organizer
      第63回日本透析医学会学術集会・総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎臓再生医療の進捗と課題 ネフロン前駆細胞から機能腎臓再生2018

    • Author(s)
      山中修一郎
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Generation of nephrons from nephron progenitor cells by the progenitor replacement system2018

    • Author(s)
      Shuichiro Yamanaka
    • Organizer
      ISN frontiers- International Society of Nephrology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Generation of interspecies chimeric nephrons from nephron progenitor cells by conditional elimination and replacement2017

    • Author(s)
      Shuichiro Yamanaka
    • Organizer
      American Society of Nephrology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel system to regenerate the kidney by replacing nephron progenitor cells in an empty niche.2017

    • Author(s)
      Shuichiro Yamanaka
    • Organizer
      ISN World Congress of Nephrology - International Society of Nephrology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 再生医療最前線 前駆細胞からネフロン再生 (シンポジウム)2017

    • Author(s)
      山中修一郎
    • Organizer
      第62回日本透析医学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Book] これまでがワカる。これからがカワる。透析療法最前線 各論 08.これからの透析医療:再生医療最前線2018

    • Author(s)
      共著 山中修一郎 監修:中元 秀友
    • Total Pages
      408
    • Publisher
      東京医学社
    • Related Report
      2018 Research-status Report

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

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