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2019 Fiscal Year Final Research Report

Elucidation of the mechanism of corneal epithelial development using SEAM as human eye development model

Research Project

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Project/Area Number 17K11480
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionOsaka University

Principal Investigator

Hayashi Ryuhei  大阪大学, 医学系研究科, 寄附講座教授 (70535278)

Project Period (FY) 2017-04-01 – 2020-03-31
Keywords多能性幹細胞 / 角膜上皮 / 表面外胚葉 / ラミニン / BMP / WNT / YAP
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.

Free Research Field

幹細胞生物学、再生医学

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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Published: 2021-02-19  

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