Hierarchical nature of metabolic reprograming to regulate differentiation of human corneal endothelial cells
| Project/Area Number |
18K16962
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Yuko Maruyama 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (60516003)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 角膜内皮細胞 / エネルギー代謝 / 細胞分化 / ミトコンドリア / ヒト角膜内皮細胞 / ミトコンドリア呼吸能 / 細胞外フラックスアナライザー / 代謝リプログラミング / 代謝産物 / TCA回路 |
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| Outline of Final Research Achievements |
It was revealed that a major functional difference between mature differentiated cells which are suitable for cell injection therapy and phase transitioned cells which do not meet the established criteria lies in the respiratory capacity of the cell, especially in mitochondrial function, by extracellular flux analysis and immunostaining. The differences in the mechanism of the production of metabolic intermediates of the TCA cycle and metabolic reprogramming between the two types of cells were also confirmed. The substrate specificity of cellular respiration was different between these cellular subpopulations. These differences in mitochondrial respiratory capacity similar to the differences between differentiated mature cells and phase transitioned cells in cultivated cells was also found between healthy and pathological corneal endothelial tissues.
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| Academic Significance and Societal Importance of the Research Achievements |
研究代表者の所属するグループは世界に先がけて培養ヒト角膜内皮細胞を用いた細胞注入再生医療を開発し、その臨床成績はNew Engl J Medに掲載された。本研究において明らかになった培養ヒト角膜内皮細胞における成熟分化細胞と相転移細胞の間のミトコンドリア機能の差違はミトコンドリア機能評価を細胞の本質的機能の指標として確立できる可能性があることを示唆している。本研究で得た培養ヒト角膜内皮細胞のエネルギー代謝の階層的変動に関する知見は培養ヒト角膜内皮細胞注入療法の最適化に貢献する。
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Report
(2 results)
Research Products
(3 results)
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[Presentation] Skewing of Mitochondrial Energy Metabolism Among Subpopulations of Cultured Human Corneal Endothelial Cells for Cell Therapy2020
Author(s)
Kohsaku Numa, Morio Ueno,Tomoko Fujita, Munetoyo Toda, Koji Ueda, Yuichi Tokuda, Atushi Mukai, Masakazu Nakano, Shigeru Kinoshita, Chie Sotozono, and Junji Hamuro
Organizer
The Association for Research in Vision and Ophthalmology）2020 Annual Meeting
Related Report
Int'l Joint Research
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