Generation of lung organ derived from rat ES cells in FGF10 deficient mice

Research Project

Project/Area Number	18H02817
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 53030:Respiratory medicine-related
Research Institution	Niigata University
Principal Investigator	Saijo Yasuo 新潟大学, 医歯学系, 教授 (10270828)
Co-Investigator(Kenkyū-buntansha)	笹岡俊邦新潟大学, 脳研究所, 教授 (50222005) 味岡洋一新潟大学, 医歯学系, 教授 (80222610)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000) Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2018: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords	肺再生 / 胚盤胞補完法 / ＥＳ細胞 / 異種間キメラ / FGF10 / ES細胞
Outline of Final Research Achievements	Blastocyst complementation enables the generation of transplantable organs from pluripotent stem cells (PSCs) in animal models. Pancreases and kidneys have been generated from PSCs via blastocyst complementation in rodent models. Here, we report the generation of lungs using mouse embryonic stem cells (ESCs) in aFgf10 Ex1mut/Ex3mut mice via blastocyst complementation. Complementation with ESCs enabled Fgf10-deficient mice to survive to adulthood without abnormalities. Not only the generated lung alveolar parenchyma, but also the interstitial portions　including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissues were largely originated from the injected ESCs. These data indicated that Fgf10 Ex1mut/Ex3mut blastocysts may provide an organ niche for lung generation, and blastocyst complementation could be applied as a viable approach to generating whole lungs.
Academic Significance and Societal Importance of the Research Achievements	臓器移植の最大の課題は、提供臓器が足りないことである。多能性幹細胞由来の肺を作ることが出来れば、この課題は解決可能である。肺を欠損するマウスの発生初期の胚盤胞に、正常なES細胞を注入してマウス産仔を得た。このマウスには正常の肺が発生しており、肺細胞の大部分はＥＳ細胞由来であった。また、このマウスは成獣まで生きることが出来た。この研究は、肺を欠損する動物において多能性幹細胞由来の肺を作り出すことができることを示した研究成果である。この研究を更にすすめ大型動物でヒト多能性幹細胞由来の肺をくつることが理論上可能であることが明らかとなった。