Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Research Abstract |
In this project, we investigated potential usage of endothelial progenitor cells (EPC) in neovascularization especially molecular mechanisms that support their adhesion to mature vascular endothelium. In the first year of the project, we were able to establish culture system of EPC in vitro. Moreover, we conducted an adhesion assay under physiological flow condition using EPC. We found that cytokine activation of vascular endothelium significantly upregulated adhesion of EPC when compared to unactivated endothelium. When we pretreated these vascular endothelium with adhesion blocking antibodies against E-selectin, ICAM 1, and VCAM-1, anti-E-selectin antibody but not other antibodies blocked adhesion of EPC to endothelium, suggesting an important role for E-selectin in EPC adhesion. In the second year, we developed a neovascularization model using ischemic hindlimb in nude mice. Injection of EPC to these mice significantly improved their neovascularization in the hindlimb as previously reported. When amount of EPC was reduced to one-fifth of the optimal number, the recovery of blood flow was significantly attenuated. However, when adenovirus containing E-selectin cDNA was introduced to express E-selectin, neovascularization was significantly restored. These data suggested that potential efficacy of E-selectin in neovascularization.
|