Establishment of a screening method for cultured human corneal endothelial cells maintaining long-term in vivo stability.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09725
• 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: Kyoto Prefectural University of Medicine
• Principal Investigator: Toda Munetoyo 京都府立医科大学, 医学(系)研究科(研究院), 特任准教授 (30550727)
• Co-Investigator(Kenkyū-buntansha): 山下 智子 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (70470250)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 角膜内皮細胞 / 再生医療

Outline of Final Research Achievements

Corneal endothelial cells (CECs) were cultured from research donor corneas and cryopreserved. The cell lots from each donor were divided into two groups based on the morphological changes, one in which cell state transition (CST) was easily induced (unstable lot) and the other in which CST was not induced (stable lot). By the DEG analysis between the two groups, some genes related to cellular senescence, adhesion, and the cytoskeleton were identified as candidate factors that could predict and evaluate the adaptability in the recipient microenvironment.
In addition, we found that the quality of cultured corneal endothelial cells from residual peripheral donor corneas was associated with the postoperative corneal endothelial density (ECD) in patients who underwent corneal transplantation. This suggests that the stability of CECs in the culture environment reflects the health of the CECs in the recipient microenvironment.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

再生医療において、移植に供される細胞は、その安全性、有効性を担保するための厳格な品質規格が求められる。一方で、エンドポイントを超えた長期間の予後成績を左右する生体内での安定性に関しては規格化されていないのが現状である。本研究の移植先微小環境に対する適応能の予測評価法の確立に向けた研究成果は、将来的に、長期予後の改善、再手術リスク軽減など、移植を受ける患者の身体的、経済的あるいは精神的負担を大きく減ずることに結び付くと考えられる。
さらに、学術的には、培養角膜内皮細胞における相転移の難易を制御する因子の解明は、ヒト角膜内皮細胞の細胞生物学的挙動を理解するためにも極めて重要である。