Elucidation of the mechanism of whole eye development and its reproduction in vitro by regulating scaffold environment using pluripotent stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03842
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Osaka University
• Principal Investigator: Hayashi Ryuhei 大阪大学, 大学院医学系研究科, 寄附講座教授 (70535278)
• Co-Investigator(Kenkyū-buntansha): 関口 清俊 大阪大学, 蛋白質研究所, 寄附研究部門教授 (50187845)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多能性幹細胞 / オルガノイド / 角膜 / YAP / 涙腺 / iPS細胞

Outline of Final Research Achievements

The purpose of this study is to elucidate the effects of cytokines, scaffolds and the surrounding environment on ocular development using pluripotent stem cell-derived organoids. Using pluripotent stem cell-derived ocular organoids, we found that the activation of YAP/TAZ signalling is required for the induction of ocular surface ectoderm such as corneal epithelium, and that BMP signalling and WNT inhibitory factors secreted from the neuroectoderm are also required. On the other hand, the inactivation of YAP/TAZ signalling was suggested to be an important process for the differentiation of neural ectoderm such as the retina. We also demonstrated for the first time that lacrimal gland organoids can be generated from human pluripotent stem cells, and that the transcription factor BARX2, Matrigel as a scaffold, and EGFR signalling are important in the early stage of lacrimal gland organoids generation.

Free Research Field

再生医学、幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によりこれまで詳細に理解されていなかったヒト眼発生とくに角膜や結膜上皮の発生機構を明らかにすることができた。さらにはこれまで報告のなかった、3次元のヒト涙腺オルガノイドを世界で初めて作製することに成功した（Hayashi R et al. Nature 2022）。本研究成果によりヒトの眼発生機構が明らかになっただけでなく、サイトカインや足場環境を調整することにより、多能性幹細胞から効率よく目的の眼細胞を誘導することが可能になり、再生医療や薬剤スクリーニング分野の発展に貢献できると考えられる。