Generation of the methods of safety evaluation for alveolar organoid transplantation
Project/Area Number |
17H05084
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Respiratory organ internal medicine
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Research Institution | Kyoto University |
Principal Investigator |
Gotoh Shimpei 京都大学, 医学研究科, 特定准教授 (50747219)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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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)
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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.
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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。
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Report
(6 results)
Research Products
(36 results)
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[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)
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[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
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[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
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[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
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