Angiogenesis: Perspectives from therapeutic angiogenesis

Peripheral arterial disease (PAD) is a major complication of systemic atherosclerosis and is a major public health threat worldwide. For patients with PAD, there are limited options for therapy, and no medications have been shown to slow progression of the disease. For patients with severe disease, open surgical procedures and endovascular techniques may relieve symptoms and prevent amputation; however, in a substantial proportion of patients, surgical and endovascular revascularization are not an option based on a patients' anatomy and/or comorbid diseases. "Stem cell therapy" covers a range of investigational approaches across various cells and delivery methods. Overall, stem cell therapy has been shown to be safe, and multiple small studies have shown benefit in pain relief, improved functional status, and decreased major amputations. Unfortunately, the results of larger trials of stem cell therapy have been largely disappointing, and many of the early studies may well have been limited by both selection bias and lack of investigator blinding. In this chapter, the embryological basis for therapy with stem cells will be reviewed, as well as major studies that set the stage for stem cell therapy as an option or those that provide important findings. The current status of stem cell therapy and future directions for this area of research will also be discussed.