Investigation of molecular mechanism of cellular-senescence of corneal endothelial cells in association with cell-culture and its application for corneal endothelial tissue engineering
Project/Area Number |
26670760
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Ophthalmology
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Research Institution | Doshisha University |
Principal Investigator |
Koizumi Noriko 同志社大学, 生命医科学部, 教授 (20373087)
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Co-Investigator(Kenkyū-buntansha) |
OKUMURA Naoki 同志社大学, 生命医科学部, 准教授 (10581499)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 角膜内皮細胞 / 再生医療 / 細胞老化 / p38 MAPキナーゼ / ラミニン / 炎症性サイトカイン / p38MAPキナーゼ阻害剤 / SASP / 細胞外マトリクス / インテグリン |
Outline of Final Research Achievements |
We have recently started a Japanese clinical trial of a cell-based therapy for treating corneal endothelial dysfunction, yet corneal endothelial cell (CEC) senescence during culture associated with cell density (CD) drop is a serious obstacle in obtaining large quantities of cells for clinical use. The aim of this study was to examine the mechanism of cellular-senescence of human CECs in culture and develop a new culture system for the clinical application of cultivated HCEC transplantation. We showed that laminin-511 is expressed in the Descemet’s membrane and laminin-511-E8 fragment enhances the adhesion and proliferation of HECE in culture. Our study also revealed that p38MAPK signaling might be activated by culture-condition-related cell stress that induces senescence-associated secretory phenotype, and that p38MAPK inhibition enables CECs culture with maintaining high CD and functional phenotype, thus indicating its usefulness for corneal endothelial regenerative medicine.
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Report
(3 results)
Research Products
(23 results)
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[Presentation] 培養角膜内皮細胞移植の治療効果に対する細胞密度の影響.2016
Author(s)
日下部綾香, 奥村直毅, 平野浩惇, 井上亮太, 岡崎友吾, 角谷和哉, 木下茂, 小泉範子
Organizer
角膜カンファランス2016 第40回日本角膜学会総会 第32回日本角膜移植学会
Place of Presentation
長野, 軽井沢プリンスホテルウエスト
Year and Date
2016-02-18
Related Report
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[Presentation] 角膜内皮再生医療.2016
Author(s)
小泉範子
Organizer
第39回日本眼科手術学会学術総会
Place of Presentation
福岡, 福岡国際会議場
Year and Date
2016-01-31
Related Report
Invited
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