Cell Therapy for Critical Limb Ischemia

Peripheral arterial disease (PAD) is a common disorder and a major cause of morbidity and mortality.1 The most severely affected patients, with rest pain, ulcerations, or gangrene, are given a diagnosis of critical limb ischemia (CLI). These patients have a particularly poor prognosis, with high rates of limb amputation and mortality. Despite improvements in medical therapy for atherosclerosis and associated comorbidities as well as improvements in interventional and surgical techniques to improve limb perfusion, CLI continues to carry a major risk of limb amputation.2,3 A significant portion of patients with CLI are considered “no option” for revascularization, and no medical therapy has been shown to be capable of reducing the need for amputation. Therefore, novel therapies are needed to treat this disorder.Articles see p 15 and 26In the late 1990s, there was a paradigm shift in our understanding of the mechanisms for neovascularization in adult mammals. Previously, it was thought that angiogenesis (ie, the sprouting of new vessels from previously existing vasculature) was the only means available for the formation of new vessels in adults. The discovery of bone marrow-derived circulating progenitor cells capable of contributing to differentiation into endothelial cells and contributing to neovascularization of ischemic tissue introduced the concept of postnatal vasculogenesis (ie, the formation of vessels de novo using the building blocks of progenitor cells).4,5 Preclinical studies then provided evidence that a variety of stem and progenitor cell types, delivered locally into ischemic tissue, could exert therapeutic effects in models of ischemia.6–8 Subsequently, a new approach to the treatment of ischemic conditions has emerged and is rapidly evolving, with investigators advancing the use of progenitor cell-based therapies in patients with advanced ischemic conditions.9,10The therapeutic use of progenitor cells poses certain unique …