Constrction and analysis of limbal niche in the corneal organoids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09708
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Tokyo Dental College
• Principal Investigator: Higa Kazunari 東京歯科大学, 歯学部, 講師 (60398782)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オルガノイド

Outline of Final Research Achievements

Human corneal epithelial stem cells are thought to be localized in the limbus around the cornea, forming the corneal epithelium. However, human corneal epithelial stem cells have not been reported to exist in the central cornea.
In this study, to investigate the usefulness of the central corneal epithelium as a cell source for corneal epithelial regeneration, we prepared organoids from the central cornea and transplanted them into a rabbit limbal deficiency model.　Corneal organoids that maintained undifferentiated and proliferative properties similar to those of limbal organoids were formed. Furthermore, when organoids prepared from the central cornea were transplanted into a limbal dysfunction model, the epithelium of the transplanted organoids were continuously observed from the organoid transplantation site to the cornea. These cells could be supplied to the cornea to form the epithelium, suggesting that they may be useful as a cell source for corneal epithelial regeneration.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

これまでに申請者が確立してきた角膜輪部オルガノイド培養法は他の上皮細胞分離法に比べ細胞周囲の環境を崩さずに採取可能であり、幹細胞-ニッチの環境を維持しながら長期に培養が可能であることがわかってきた。本研究では、これまで積み重ねてきた我々の培養技術を応用し、分化した角膜上皮細胞から幹細胞-ニッチを新たに構築可能な角膜オルガノイドの作成法を確立することができた。これは、輪部機能不全を伴った難治性の疾患に対する角膜上皮幹細胞の新たな細胞供給源として期待されるだけでなく、輪部機能で重要な幹細胞ニッチの供給源としても期待される。