| Project/Area Number |
19K09299
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | オルガノイド / 肺の再生 / 間葉系前駆細胞 / 共培養 / 上皮－間充織相互作用 / iPS細胞 / 中胚葉 / 内胚葉 / 分化誘導 / 間充織 |
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| Outline of Research at the Start |
再生医療への応用を目指し、これまでにもiPS細胞をまず内胚葉に分化誘導し、そこから胎児期の肺に近い性質を持つ肺様体を作り出したという報告などがある。しかし未だ機能する肺を作れたという報告はない。実はそれらの研究には、臓器構築には内胚葉由来の細胞だけでなく、中胚葉由来の細胞も必要であるという観点が欠けていた。正常な肺の発生過程では、これら二つの細胞集団の相互作用が重要なことがわかっている。そこでこの研究では、iPS細胞から中胚葉へと分化誘導した細胞を、同じくiPS細胞由来の内胚葉の細胞と共培養して、より新生児肺に近い組織構築を目指す。
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| Outline of Final Research Achievements |
Making organs from human pluripotent stem cells (iPSC) is a challenging approach for developmental biology, cell biology and regenerative medicine.
There are several reports that describe induction of organoid such as gastric, intestinal, pancreatic, liver bud and recently lung. In most of the cases, they first tried to induce endoderm, then further differentiation of endoderm and mesenchyme which supports endoderm. However, in normal development, most of the mesenchyme which works for maintenance of differentiated endoderm is derived from mesoderm. We thought that this discrepancy introduces limitation for further differentiation. Based on this idea, we developed step-wise protocol to make highly organized lung form iPSC. As a first step, we attempted to re-produce the lung organoid that was reported before. In the second step, we induced lung mesenchyme from mesoderm which is derived from iPSC. In the last step, these tissues were combined to produce mature lung.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで多能性幹細胞を二つの異なる胚葉に分化させ、それらを組み合わせて培養する研究はほとんど行われておらず、この手法の有用性が明らかとなったことには学術的意義がある。また、自己あるいは組織抗原の一致するiPS細胞から人工的に臓器を作成することが可能になれば、臓器移植の代替手段の開発につながることが期待できる。
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