Development of a method to induce differentiation from human iPS cells to the kidney using organ niches

• Project/Area Number: 16K09630
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Matsumoto Kei 東京慈恵会医科大学, 医学部, 助教 (30439799)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腎臓再生医療 / 幹細胞 / 臓器ニッチ法 / 腎臓再生 / 異種移植 / 後腎移植 / 遺伝子改変動物 / iPS細胞 / 胎性臓器ニッチ法 / 再生医療 / 慢性腎不全 / 腎性貧血 / 胎生臓器ニッチ法 / 腎前駆細胞 / 間葉系幹細胞

Outline of Final Research Achievements

In order to realize kidney regeneration therapy, we have used the fetal organ niche method, in which stem cells and renal progenitor cells are injected into a heterologous fetus' renal development site to induce the differentiation to the kidney. This was reproducible between mouse and rat heterozygotes. We utilized these mice to successfully develop maternal glomeruli in the kidney using the Exo Utero injection approach to the maternal fetal kidney in vivo environment.

Academic Significance and Societal Importance of the Research Achievements

末期腎不全患者における腎代替療法には血液透析、腹膜透析、腎移植があるが、昨今の医療経済の逼迫状況や患者QOLのさらなる改善を考えると、新たな治療法の開発が急務であり、第４の治療法として腎再生医療が期待されている。
本研究は腎臓再生医療を目指す上で重要となる基盤技術の確立として、ヒトiPS細胞から分化誘導した腎前駆細胞を移植する臓器ニッチの改善を目指して小動物における研究を行い、一定の良好な結果を得られた。
将来のヒト臨床応用を目指した大型化、さらなる効率化を目指して行く必要がある。

Research Products

• [Journal Article] In vivo regeneration of interspecies chimeric kidneys using a nephron progenitor cell replacement system (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Mesangial cell regeneration from exogenous stromal progenitor by utilizing embryonic kidney (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Kidney Regeneration in Later-Stage Mouse Embryos via Transplanted Renal Progenitor Cells (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] 臓器発生ニッチを用いたヒトiPS細胞から腎への分化誘導法の開発 (2019)
  • Author(s): 松本啓、藤本俊成、田尻進、山中修一郎、宮崎陽一、横尾隆
  • Journal Title: 発達腎研究会誌 Volume: 27 Pages: 35-39
• [Journal Article] Regenerative potential of induced pluripotent stem cells derived from patients undergoing haemodialysis in kidney regeneration (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration (2018)
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 腎臓再生医療へ向けてのコモン・マーモセットを用いたin vivo ブタ腎発生の検討 (2019)
  • Author(s): 松本啓，岩井聡美，松成ひとみ，藤本俊成，斎藤弥積，高村毅， 高瀬健太郎，田尻進，山中修一郎，横手伸也，福井亮，小林英司，長嶋比呂志，横尾隆
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] Optimal route of diphtheria toxin administration to eliminate native nephron progenitor cells in vivo for kidney regeneration (2018)
  • Author(s): Shohei Fukunaga, Shuichiro Yamanaka, Toshinari Fujimoto, Susumu Tajiri, Taketo Uchiyama, Kei Matsumoto, Takafumi Ito, Kazuaki Tanabe, Takashi Yokoo
  • Organizer: 55回欧州腎臓学会議・欧州透析移植学会議 ２０１８
  • Int'l Joint Research
• [Presentation] Exo utero method to regenerate nephrons from nephron progenitor cells in the living fetus (2018)
  • Author(s): Shuichiro Yamanaka , Yatsumu Saitou, Toshinari Fujimoto , Susumu Tajiri, Tsuyoshi Takamura, Kei Matsumoto, Takashi Yokoo
  • Organizer: アメリカ腎臓学会２０１８
  • Int'l Joint Research
• [Presentation] マウス腎発生ニッチを用いたラットネフロンの再生：in vivoでの異種間ネフロン再生の検討 (2018)
  • Author(s): 藤本俊成、山中修一郎、田尻進、松本啓、福永昇平、横尾隆
  • Organizer: 第20回 日本異種移植研究会
• [Presentation] マウス後腎内でのラットネフロンの再生：in vivoでの異種間ネフロン再生の検討 (2018)
  • Author(s): 藤本俊成、山中修一郎、田尻進、松本啓、福永昇平、岡野ジェイムス洋尚、横尾隆
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] Establishment of the fetal nephron progenitor cells elimination in the uterus using iDTR system (2018)
  • Author(s): Shohei Fukunaga, Shuichiro Yamanaka, Toshinari Fujimoto, Susumu Tajiri, Taketo Uchiyama, Kei Matsumoto, Takashi Yokoo
  • Organizer: ISN FRONTIERS2018
  • Int'l Joint Research
• [Presentation] In vivo regeneration of nephrons between different species under the administration of the optimal immunosuppressive agent using the drug-induced cell elimination system (2018)
  • Author(s): Toshinari Fujimoto, Shuichiro Yamanaka, Susumu Tajiri, Kei Matsumoto, Shohei Fukunaga, Takashi Yokoo
  • Organizer: ISN FRONTIERS2018
  • Int'l Joint Research
• [Presentation] iDTR systemを用いた母胎内胎児腎前駆細胞除去モデルの作成 (2018)
  • Author(s): 福永 昇平、山中 修一郎、藤本 俊成、田尻 進、松本 啓、横尾 隆
  • Organizer: 日本医工学治療学会 第３４回学術大会
• [Presentation] 前駆細胞置換による腎臓再生 (2017)
  • Author(s): 山中修一郎、田尻進、藤本俊成、松本啓、岡野ジェイムス洋尚、横尾隆
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2017-03-07
• [Presentation] カフ法を用いた異種心移植モデルによる免疫抑制療法の検討 (2017)
  • Author(s): 藤本俊成、松本啓、田尻進、山中修一郎、福永昇平、横手伸也、後藤花子、Kim Bum Soo、小林英司、横尾隆
  • Organizer: 第19回 日本異種移植研究会
  • Place of Presentation: 京都メルパルクホール
  • Year and Date: 2017-02-25
• [Presentation] Generation of interspecies chimeric nephrons from nephron progenitor cells by conditional elimination and replacement (2017)
  • Author(s): Shuichiro Yamanaka, Kei Matsumoto, Susumu Tajiri, Toshinari Fujimoto, Shohei Fukunaga, Takashi Yokoo
  • Organizer: American society of Nephrology KIDNEYWEEK 2017
  • Int'l Joint Research
• [Presentation] Regeneration of rat nephrons in the mouse metanephros: in vivo regeneration of nephrons between different species under the administration of optimal immunosuppressive agents (2017)
  • Author(s): Toshinari Fujimoto, Shuichiro Yamanaka, Susumu Tajiri, Kei Matsumoto, Shohei Fukunaga, Takashi Yokoo
  • Organizer: American society of Nephrology KIDNEYWEEK 2017
  • Int'l Joint Research
• [Presentation] 「胎生臓器ニッチ法を用いた腎臓再生」 (2017)
  • Author(s): 松本 啓、横尾 隆
  • Organizer: 第105回日本泌尿器科学会総会
  • Invited