Cell-Based Therapies for Peripheral Arterial Disease

Peripheral arterial disease (PAD) is commonly referred to ischemia of extremities secondary to atherosclerotic occlusion. More than 25 million patients suffer from PAD in the developed countries [1-5]. An additional cause of PAD is vasculitis including thromboangitis obliterance (TAO) (Buerger’s disease), which can also lead to severe limb ischemia. Chronic critical limb ischemia (CLI) is defined as the end-stage of lower limb ischemia. The clinical manifestations consist of rest pain and/or skin ulceration or gangrene. The annual incidence of CLI is estimated to be 500-1,000 cases per million people and an estimated 250,000 major amputation are performed annually in the United States and Europe, resulting in a significant socioeconomic burden and severe reduction in quality of life [5]. Prognosis of the CLI patients is quite poor. The 1-year mortality and major amputation rate are reported to be 25% and 30%, respectively [5]. Currently, revascularization of the ischemic limb with surgical bypass techniques or endovascular approaches is believed to be the best option for limb salvage. However, 25-40% of patients with CLI are not candidates for either of these options due to a lack of autologous vein graft, extensive lesions in the tibial and peroneal arteries or medical co-morbidity [5-7]. Therefore, new strategies for blood flow recovery are urgently required for such no-option patients with CLI. The challenge to improve blood flow to CLI has provoked extensive research programs and numerous innovative approaches in the fields of molecular biology and pharmacology.