[Therapeutic angiogenesis of critical lower limb ischemia. Review of the literature and prospects of research on stem cells]

Chronic peripheral arterial disease affects up to 15% of adults over the age of 55 years; critical limb ischemia represents the most dramatic clinical outcome. Patients with chronic critical limb ischemia who are not candidate for surgical or percutaneous revascularization have impending limb loss; those who benefit from successful revascularization suffer from high rate of recurrent symptoms or revision surgery or progressive amputations. In these patients no medical treatment is considered effective for rest pain or ulcer healing. Therapeutic angiogenesis, which has the goal to achieve the process of new blood vessel formation via the administration of growth factors, has become a new promising hope. The discovery of the possibility of inducing sprouting of new vessels from preexisting vasa (angiogenesis) or the in situ differentiation of endothelial cells from stem cell precursors (vasculogenesis) have open new lease on life. However, a careful analysis of experimental results achieved in animal models is required before proposing for clinical setting. Although a major concern is that most of the experimental work has been done on animal models that do not represent the clinical process, benefit from growth factor administration or stem cell therapy has been proven in clinical trials, suggesting the importance of this new research frontier. This literature review is aimed to examine potential applications of therapeutic angiogenesis to treat critical limb ischemia with particular attention to angiogenesis obtained with stem cells.