Investigation of molecular mechanism of cellular-senescence of corneal endothelial cells in association with cell-culture and its application for corneal endothelial tissue engineering

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670760
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Doshisha University
• Principal Investigator: Koizumi Noriko 同志社大学, 生命医科学部, 教授 (20373087)
• Co-Investigator(Kenkyū-buntansha): OKUMURA Naoki 同志社大学, 生命医科学部, 准教授 (10581499)
• Project Period (FY): 2014-04-01 – 2016-03-31
• 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

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.

Free Research Field

再生医療、医工学、眼科学