Therapeutic angiogenesis. Devising new strategies based on past experiences.

Therapeutic angiogenesis improves tissue ischemia by supplementing and supporting the intrinsic process of angiogenesis. Besides direct administration of angiogenic growth factor proteins, injection of naked DNA, non-viral vectors and viral vector constructs carrying angiogenic genes have been used. A novel approach is to achieve therapeutic angiogenesis through cell mediated gene transfer. Genetically modulated cells carrying exogenous genes encoding for angiogenic factors and the cells with inherent ability to secrete angiogenic cytokines, such as bone marrow stem cells, embryonic stem cells and endothelial progenitor cells, have been used to achieve revascularization. This review discusses proof of the concept pre-clinical studies and phase-I/II human trials using VEGF, and cellular angiogenesis at length in the light of the literature and analyzes the problems and considerations of these approaches as a treatment strategy in the clinical perspective for the treatment of ischemic heart disease.