2013 Fiscal Year Final Research Report

Therapeutic neovascularization targeting Notch signaling

Research Project

Project/Area Number	23591097
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Circulatory organs internal medicine
Research Institution	Chiba University
Principal Investigator	TATENO Kaoru 千葉大学, 医学部附属病院, 助教 (20532758)
Co-Investigator(Renkei-kenkyūsha)	MINAMINO Tohru 新潟大学, 医歯学総合研究科, 教授 (90328063)
Project Period (FY)	2011 – 2013
Keywords	分子血管病態学 / 再生医療
Research Abstract	Peripheral blood mononuclear cell implantation is a promising method to treat critical limb ischemia. Nonetheless, 30% of the cases are non-responding. We found that Notch ligand expression in these patients was down regulated. Likewise, mice models deleting Notch ligands or receptors from donor cells or host ischemic muscles, respectively, revealed that Notch signaling components are critical in the mechanism of the therapy. We employed mice models for non-responding patients, i.e. diabetes or aged mice, and found that Notch signaling was attenuated following limb ischemia. Addition of Jagged-1, but not Dll-4, overexpressing cells to these models helped ischemia to heal more adequately. These results warrant us to further deploy a Notch targeting therapy for previously the non-responding patients.