| Project/Area Number |
17K11480
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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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| Research Field |
Ophthalmology
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| Research Institution | Osaka University |
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Principal Investigator |
Hayashi Ryuhei 大阪大学, 医学系研究科, 寄附講座教授 (70535278)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 多能性幹細胞 / 角膜上皮 / 表面外胚葉 / ラミニン / BMP / WNT / YAP / 眼発生 / 分化 / ECM / 神経堤 / 角膜 |
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| Outline of Final Research Achievements |
The purpose of this study is to elucidate the signalling mechanisms derived from growth factors and ECMs that contribute to corneal epithelial development by using a human eye development model, SEAM. First, knock-in iPS cell line labelled with EGFP for the p63 gene was established. This KI iPS cell line was used for SEAM induction and demonstrated that in addition to intrinsic BMP-signalling, WNT-signal inhibition is essential for corneal epithelium induction. Regarding ECMs, only laminin isoform 511, which is widely expressed in ocular tissues and has strong integrin-binding capacity was able to induce typical SEAM formation, and that YAP-mediated signals derived from integrin-laminin binding are important for the developmental branching of neuroectoderm and surface ectoderm, including corneal epithelium.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではヒトの眼発生を模倣した細胞モデルであるSEAMを用いて、特に角膜上皮の発生、分化の機序について調べた。角膜上皮は再生医療のための細胞源としてのニーズが高く、我々もiPS細胞を用いた角膜上皮再生医療の開発に取り組んできた。一方で、iPS細胞から角膜上皮を安定的かつ効率的に分化誘導することは容易ではない事も明らかとなってきた。本研究で得られた成果により角膜がどのように発生・分化するのかの理解が深まったことで、角膜上皮を得るための方法が改良され、より安定的かつ効率的に角膜上皮を得ることが可能となった。これにより、再生医療の課題でもあるコスト削減や安全性を高めることが可能になると期待される。
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