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Generation of the methods of safety evaluation for alveolar organoid transplantation

Research Project

Project/Area Number 17H05084
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionKyoto University

Principal Investigator

Gotoh Shimpei  京都大学, 医学研究科, 特定准教授 (50747219)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Keywords肺 / ヒトiPS細胞 / 移植 / オルガノイド / 肺胞 / iPS細胞 / 再生医学 / 細胞・組織
Outline of Final Research Achievements

Through this project, the methods of generating human induced pluripotent stem (iPS) cell-derived alveolar epithelial cells and their long-term culture have been established. The differentiation process from the lung progenitor cells to alveolar epithelial cells was delineated at the single-cell level. Not only human iPS cell-derived alveolar type II (iAT2) cells but also alveolar type I (iAT1) cells were identified. Each transcriptome was compared and thereby the method of directing differentiation from iAT2 to iAT1 cells was established. On the other hand, iAT2 cells can possess and secrete lamellar bodies, organelles to restore pulmonary surfactant. Gene editing technology has made it possible to establish disease modeling of rare hereditary diseases in a dish. And a method of safe transfer of alveolar organoids intratracheally to mouse was developed and the iPSC-derived cells were successfully engrafted on the living mouse lung without generating tumor-like lesion.

Academic Significance and Societal Importance of the Research Achievements

ヒト由来肺胞上皮細胞は長年、研究利用の難しい細胞だったが、多能性幹細胞を用いることで、必要時に必要な数のヒト肺胞上皮細胞を分化誘導して研究利用が可能になった。さらに遺伝子改変も行えるようになったことで、疾患研究への波及効果も見出せるようになった。さらにヒトiPS細胞由来の肺胞上皮細胞をマウスに定着させることもでき、特に腫瘍性変化を伴うことはなかった。これらの成果により呼吸器における再生医療や創薬に向けてさらなる研究の発展を期待できるようになった。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Products Report
  • Research Products

    (36 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (31 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition2020

    • Author(s)
      Kanagaki Shuhei、Ikeo Satoshi、Suezawa Takahiro、Yamamoto Yuki、Seki Masahide、Hirai Toyohiro、Hagiwara Masatoshi、Suzuki Yutaka、Gotoh Shimpei
    • Journal Title

      STEM CELLS

      Volume: 39 Issue: 2 Pages: 156-169

    • DOI

      10.1002/stem.3302

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A method of generating alveolar organoids using human pluripotent stem cells2020

    • Author(s)
      Yamamoto Yuki、Korogi Yohei、Hirai Toyohiro、Gotoh Shimpei
    • Journal Title

      Methods in Cell Biology

      Volume: 159 Pages: 115-141

    • DOI

      10.1016/bs.mcb.2020.02.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In?Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2?Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids2019

    • Author(s)
      Korogi Yohei、Gotoh Shimpei、Ikeo Satoshi、Yamamoto Yuki、Sone Naoyuki、Tamai Koji、Konishi Satoshi、Nagasaki Tadao、Matsumoto Hisako、Ito Isao、Chen-Yoshikawa Toyofumi F.、Date Hiroshi、Hagiwara Masatoshi、Asaka Isao、Hotta Akitsu、Mishima Michiaki、Hirai Toyohiro
    • Journal Title

      Stem Cell Reports

      Volume: 12 Issue: 3 Pages: 431-440

    • DOI

      10.1016/j.stemcr.2019.01.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term expansion of alveolar stem cells derived from human iPS cells in organoids2017

    • Author(s)
      Yamamoto Yuki、Gotoh Shimpei、Korogi Yohei、Seki Masahide、Konishi Satoshi、Ikeo Satoshi、Sone Naoyuki、Nagasaki Tadao、Matsumoto Hisako、Muro Shigeo、Ito Isao、Hirai Toyohiro、Kohno Takashi、Suzuki Yutaka、Mishima Michiaki
    • Journal Title

      Nature Methods

      Volume: 14 Issue: 11 Pages: 1097-1106

    • DOI

      10.1038/nmeth.4448

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト多能性幹細胞から分化誘導した気道・肺胞オルガノイドの応用2021

    • Author(s)
      後藤慎平
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] シングルセル解析で見えてきたiPS細胞由来I型肺胞上皮細胞2020

    • Author(s)
      後藤慎平
    • Organizer
      第60回日本呼吸器学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 分子生物学的視点からみたCOVID-19肺炎の病態 重症化のメカニズム2020

    • Author(s)
      後藤慎平
    • Organizer
      第60回日本呼吸器学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 呼吸器におけるiPS細胞研究2019

    • Author(s)
      後藤慎平
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Recapitulating functional lung cells by using human iPS cells2019

    • Author(s)
      後藤慎平
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Applications of functional lung epithelial cells derived from human pluripotent stem cells.2019

    • Author(s)
      Shimpei Gotoh
    • Organizer
      American Thoracic Society Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞を用いた肺オルガノイドからの呼吸器疾患モデリング2019

    • Author(s)
      後藤慎平
    • Organizer
      千里ライフサイエンスセミナーN2
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の呼吸器分野への応用2019

    • Author(s)
      後藤慎平
    • Organizer
      第72回日本胸部外科学会 定期学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Assessment of bipotency of expanded human induced pluripotent stem cell-derived NKX2.1+ lung progenitor cells to be differentiate into both airway and alveolar epithelial cells.2019

    • Author(s)
      Satoshi Ikeo, Shimpei Gotoh, Yohei Korogi, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Yuki Yamamoto, Toyohiro Hirai
    • Organizer
      International Society for Stem Cell Research 16th Annual Meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] Application of human induced pluripotent stem cells to disease modelling of primary ciliary dyskinesia.2019

    • Author(s)
      Naoyuki Sone, Shimpei Gotoh, Satoshi Konishi, Koji Tamai, Satoshi Ikeo, Yohei Korogi, Koichi Igura, Toyohiro Hirai.
    • Organizer
      Gordon Research Conference
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characterization of human alveolar cells derived from HPS2 patient-derived iPS cells.2019

    • Author(s)
      Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Tadao Nagasaki, Isao Asaka, Akitsu Hotta, Toyohiro Hirai.
    • Organizer
      Epithelial Mesenchymal Interactions in Lung Development and Fibrosis Conference (Fusion Conferences)
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いた呼吸器疾患の病態解明2019

    • Author(s)
      後藤 慎平
    • Organizer
      第139回 日本薬学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞由来肺胞オルガノイドによるHermansky-Pudlak症候群2型のモデリング2019

    • Author(s)
      興梠陽平、後藤慎平、池尾聡、山本佑樹、曽根尚之、玉井浩二、小西聡史、長崎忠雄、浅香勲、堀田秋津、平井豊博
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Applications of human pluripotent stem cells for lung research.2018

    • Author(s)
      後藤 慎平
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] COPD治療を目指したヒトiPS細胞の技術2018

    • Author(s)
      後藤 慎平
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A model of human developing alveoli involving expandable alveolar epithelial type II cells derived from iPS cells.2018

    • Author(s)
      Yuki Yamamoto, Shimpei Gotoh, Yohei Korogi, Masahide Seki, Satoshi Konishi, Satoshi Ikeo, Naoyuki Sone, Tadao Nagasaki, Hisako Matsumoto, Shigeo Muro, Isao Ito, Toyohiro Hirai, Takashi Kohno, Yutaka Suzuki, Michiaki Mishima
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Disease modeling of primary ciliary dyskinesia using human induced pluripotent stem cells.2018

    • Author(s)
      Naoyuki Sone, Shimpei Gotoh, Satoshi Konishi, Koji Tamai, Satoshi Ikeo, Yohei Korogi, Koichi Igura, Toyohiro Hirai.
    • Organizer
      International Society for Stem Cell Research Annual Meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] Transplantation study of human alveolar stem cells derived from iPS cells.2018

    • Author(s)
      Yuki Yamamoto, Shimpei Gotoh, Satoshi Ikeo, Yohei Korogi, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Toyohiro Hirai.
    • Organizer
      TERMIS World Congress
    • Related Report
      2018 Annual Research Report
  • [Presentation] Application of human iPS cell technologies for lung research.2018

    • Author(s)
      後藤 慎平
    • Organizer
      第54回日本肺サーファクタント・界面医学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Recapitulating alveolar epithelial type 2 cell dysfunction in Hermansky-Pudlak Syndrome type 2 patient-derived induced pluripotent stem cells2018

    • Author(s)
      Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Isao Asaka, Akitsu Hotta, Toyohiro Hirai
    • Organizer
      第54回日本肺サーファクタント・界面医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Generation and applications of human iPS cell-derived lung epithelial cells.2018

    • Author(s)
      Shimpei Gotoh
    • Organizer
      23rd Congress of the Asian Pacific Society of Respirology
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] シングルセル解析で見えてきたin vitro 分化の不均一性と整合性2018

    • Author(s)
      後藤 慎平
    • Organizer
      第17回再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Induction of functional lung epithelial cells from human pluripotent stem cells2018

    • Author(s)
      後藤 慎平
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞を用いた肺胞オルガノイド長期培養系の確立とその応用2018

    • Author(s)
      山本 佑樹, 後藤 慎平, 興梠 陽平、関 真秀、小西 聡史、池尾 聡、曽根 尚之、長崎 忠雄、松本 久子、室 繁郎、伊藤 功朗、平井 豊博、河野 隆志、鈴木 穣、三嶋 理晃
    • Organizer
      第17回再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト多能性幹細胞由来の呼吸器上皮細胞の有用性2017

    • Author(s)
      後藤 慎平
    • Organizer
      第40回日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] In vitro disease modeling of alveolar phenotype caused by AP3B1 deficiency using human induced pluripotent stem cells2017

    • Author(s)
      Yohei Korogi, Shimpei Gotoh, Yuki Yamamoto, Satoshi Konishi, Tadao Nagasaki, Naoyuki Sone, Satoshi Ikeo, Hisako Matsumoto, Shigeo Muro, Isao Ito, Isao Asaka, Akitsu Hotta, Toyohiro Hirai
    • Organizer
      International Society for Stem Cell Research (ISSCR) 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Long-term expansion of alveolar stem cells derived from human iPS cells by forming organoids2017

    • Author(s)
      Yuki Yamamoto, Shimpei Gotoh, Yohei Korogi, Masahide Seki, Satoshi Konishi, Satoshi Ikeo, Naoyuki Sone, Tadao Nagasaki, Hisako Matsumoto, Shigeo Muro, Isao Ito, Toyohiro Hirai, Takashi Kohno, Yutaka Suzuki, Michiaki Mishima.
    • Organizer
      CiRA 2017 International Symposium
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトiPS細胞由来肺胞オルガノイドによるHermansky-Pudlak症候群2型のモデリング2017

    • Author(s)
      興梠陽平、後藤慎平、山本佑樹、池尾 聡、曽根尚之、小西聡史、玉井浩二、平井豊博
    • Organizer
      第53回日本肺サーファクタント関連(界面)医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞由来肺胞オルガノイドによるHermansky-Pudlak症候群2型のモデリング2017

    • Author(s)
      興梠陽平、後藤慎平、山本佑樹、小西聡史、長崎忠雄、曽根尚之、池尾聡、松本久子、室繁郎、伊藤功朗、浅香勲、堀田秋津、平井豊博
    • Organizer
      第57回 日本呼吸器学会学術講演会 細胞・分子生物学学術部会(CMB)サテライトミーティング 呼吸器基礎研究を加速するための若手研究会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いたⅡ型肺胞上皮細胞の量産化を目指して2017

    • Author(s)
      山本佑樹、後藤慎平、興梠陽平、小西聡史、池尾聡、曽根尚之、玉井浩二、平井豊博
    • Organizer
      第53回日本肺サーファクタント関連医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オルガノイド形成下におけるヒトiPS細胞由来肺胞幹細胞の長期培養とその細胞不均一性2017

    • Author(s)
      山本佑樹、後藤慎平、興梠陽平、関真秀、小西聡史、池尾聡、曽根尚之、長崎忠雄、松本久子、室繁郎、伊藤功朗、平井豊博、河野隆志、鈴木穣、三嶋理晃
    • Organizer
      第40回日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 肺間葉細胞の製造方法および肺間葉細胞2022

    • Inventor(s)
      後藤 慎平、玉井 浩二
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-014212
    • Filing Date
      2022
    • Related Report
      Products Report
    • Overseas

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Published: 2017-04-28   Modified: 2023-03-30  

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