| Project/Area Number |
18K15921
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Niigata University |
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Principal Investigator |
Zhou Qiliang 新潟大学, 医歯学系, 助教 (10770232)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺再生 / 胚盤胞補完法 / 多能性幹細胞 / ES細胞 |
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| Outline of Final Research Achievements |
We succeeded in the generation of lungs using mouse embryonic stem cells (ESCs) in apneumic Fgf10 Ex1mut/Ex3mut mice by blastocyst complementation. Complementation
with ESCs enables Fgf10-deficient mice to survive to adulthood without abnormalities. Both the generated lung alveolar parenchyma and the interstitial portions, including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissue, largely originate from the injected ESCs.
Our data suggest that Fgf10 Ex1mut/Ex3mut blastocysts provide an organ niche for lung generation and that blastocyst complementation could be a viable approach for generating whole lungs.
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| Academic Significance and Societal Importance of the Research Achievements |
多くの重症肺疾患においては肺移植しか救命の道がない。しかし、絶対的なドナー不足と移植後の免疫拒絶が深刻な問題となる。多能性幹細胞を用いる肺臓器作成ができれば、上記問題の克服が可能となる。しかし肺は複雑な3次元構造を持ち、かつ多数の細胞種からなる複雑な臓器であり、in vitro での移植に耐えうる肺臓器の再構築は極めて難しいと考えられる。本研究の胚盤胞補完法を用いるin vivoでの肺再生技術を発展させ、異種間キメラや大型動物における肺臓器創出技術の確立への展開することにより、肺移植を目指すための肺臓器再生研究または肺疾患解明や新薬開発のためのモデル動物開発に大きく貢献するものと期待される。
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