Ylä-Herttuala Seppo
AlVirtanen Institute, University of Kuopio, PO Box 1627, Kuopio FIN-70211, Finland.
Curr Opin Mol Ther. 2006 Aug;8(4):295-300.
Therapeutic angiogenesis is a promising new concept for the treatment of tissue ischemia and other related medical conditions or processes, such as wound healing. Members of the vascular endothelial growth factor (VEGF) family are among the most powerful modulators of vascular growth; they regulate vascular growth and maintenance during embryogenesis and in adults. Despite progress in basic research and preclinical animal studies of therapeutic angiogenesis, significant problems still exist in translating experimental findings into beneficial clinical approaches. This review summarizes these problems and highlights recent findings in the field of therapeutic angiogenesis using VEGF and other factors, with special reference to potential clinical applications. Also, in order to better optimize vectors, doses and treatment approaches, it is proposed that the analysis of new parameters is introduced. These parameters consist of: i) spreading throughout and reaching appropriate cells in the target tissue, ii) transfection efficiency, iii) expression strength, and iv) duration of expression. It is envisaged that this 'STED' analysis will aid the clinical development of gene therapy.
治疗性血管生成是治疗组织缺血及其他相关医学病症或过程(如伤口愈合)的一个很有前景的新概念。血管内皮生长因子(VEGF)家族成员是血管生长最强大的调节因子之一;它们在胚胎发育和成体中调节血管生长和维持。尽管治疗性血管生成的基础研究和临床前动物研究取得了进展,但将实验结果转化为有益的临床方法仍存在重大问题。本综述总结了这些问题,并重点介绍了使用VEGF和其他因子的治疗性血管生成领域的最新发现,特别提及了潜在的临床应用。此外,为了更好地优化载体、剂量和治疗方法,建议引入新参数分析。这些参数包括:i)在靶组织中扩散并到达合适的细胞,ii)转染效率,iii)表达强度,以及iv)表达持续时间。预计这种“STED”分析将有助于基因治疗的临床开发。