| 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 |
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| Research Field |
Ophthalmology
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| Research Institution | Doshisha University |
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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)
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| 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 |
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| 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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