Therapeutic angiogenesis in the management of critical limb ischemia: current concepts and review.

Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease. Manifestations of CLI include rest pain, ischemic ulcers, and/or gangrene. The presence of CLI frequently leads to amputation, and furthermore, patients with CLI are at an increased risk of cardiovascular events including death. Treatment options for CLI when revascularization is not possible are extremely limited. Therapeutic angiogenesis is a promising new tool in the management of CLI. There is a growing body of evidence demonstrating the safety and efficacy of therapeutic angiogenesis with gene and cell therapy. Many factors must be considered in formulating clinically efficacious gene and/or cell therapies. The dosing regimen, route of delivery, and choice of growth factor or cell population must be decided. Although the optimal regimen of therapeutic angiogenesis has yet to be identified, building on the knowledge gained from the early pioneering studies may help to identify the best combination.