Angiogenic cell therapy for critical limb ischemia: an update on concepts and trials

Therapeutic neovascularization is a novel approach used to salvage critically ischemic limbs that are not amenable to conventional treatments. Initial efforts were based on single injections of angiogenic factors but there is now a realization that delivering angiogenic cells is more likely to achieve effective revascularization. Clinical studies to date have mostly used mixtures of mononuclear cells harvested from the bone marrow or peripheral blood. The modest results achieved with these cells, only a proportion of which are angiogenic, has stimulated a search for more potent cell types. Preclinical studies have identified several candidates, including adipose derived, embryonic and induced pluripotent stem cells. This review provides an update on the current status of angiogenic cell therapy for the ischemic limb and outlines efforts aimed at enhancing the clinical efficacy of treatments.