Hierarchical Regulation of Multiple Angiogenic Growth Factors During 'Functional' Angiogenesis In Vivo

点击翻译按钮获取中文摘要

In this project, we focused onto the basic mechanisms which determine 'functional and physiological' or 'non-functional and pathological' angiogenesis in vivo using extremely efficient viral vector, namely recombinant Sendai virus(SeV).We clarified that ;(1)During angiogenic process, harmonized regulation of the expression of multiple angiogenic factors, namely 'timing' and 'expression level', is required for neovessels to get their function ; unbalanced 'timing' and 'expression level' of angiogenic factors resulted in 'pathological' angiogenesis.(2)Basic fibroblast growth factor(FGF-2) is one of best polypeptide to induce 'functional' angiogenesis. During this process, FGF-2 regulates multistep activation of multiple angiogenic growth factors.(3)Mesenchymal cells, including pericytes, smooth muscle cells, and fibroblasts, are absolutely required to form 'functional' angiogenesis.These findings have been published more than 10 internationally recognized peer-reviewed journals(Circ Res,3 papers, J Immunol, Gene Ther, Hum Gene Ther, etc).According to these findings, we now started a project for "Phase I and IIa clinical study for angiogenic gene therapy using recombinant SeV expressing human FGF-2 gene to treat subjects with critical limb ischemia". The protocol has been passed the Institutional Review Board, and now under evaluation by Governmental Gene Therapy Committee. Preparation of GMP grade vectors and biohazard room for intervention have been completed.We hope to continue the research seeking the basic mechanisms of 'functional angiogenesis' as well as 'clinical trial of angiogenic gene therapy' to perform more efficient angiogenic therapeutics.