Stem Cell Transplantation for the Treatment of Peripheral Arterial Disease

Abstract

Peripheral Arterial Disease (PAD) is a chronic occlusion of lower-extremity arteries distal to the aortic bifurcation [1, 2]. It affects 3%-12% in the general population and its frequency increases with age [1-3]. In the vast majority of patients, PAD is ascribable to atherosclerosis [1,2 ]. It is a progressive disease leading to severe haemodynamic compromise of the affected extremity and may be even limb threatening in the event of critical ischaemia [1-3]. Not only does PAD have a considerable unfavourable impact on the quality of life, but it also poses a tremendous economic burden on society [1-3] and is an ominous harbinger of high morbidity and mortality due to concomitant coronary artery disease and cerebrovascular disease [4-6]. Management of PAD may be divided into medical and surgical. The former includes risk factor modification and medical treatment [3, 5, 7, 8], while the latter comprises surgical revascularisation (bypass surgery, intraluminal angioplasty, endovascular surgery) [9-11]. Revascularisation may be divided into percutaneous transluminal angioplasty (PTA) and by-pass surgery [9, 10, 12, 13]. The former can restore adequate blood flow, while recurrence is infrequent and amputation rates are rare [9-11]. This technique yields favourable results in patients with critical limb ischaemia as well [9, 10]. By-pass graft surgery has also been extensively practised [12, 13]. Depending on the location of affected arteries, it may be performed to the femoral, popliteal or even distal arteries, such as the dorsalis pedis artery [12, 13]. However, vascular atherosclerotic lesions may diffusely affect several anatomical regions. This holds especially true for elderly and diabetic patients, who may, therefore, be poor candidates for surgical intervention [1, 14]. Regrettably, it may also apply to patients with critical limb ischaemia or those who have had prior revascularisation [1, 15]. Hence, there is an undeniable need to develop alternative therapeutic modalities to restore limb blood flow [1, 5, 15, 16]. This chapter reviews the progress achieved with autologous stem cell transplantation, an important innovation involving intramuscular and/or intra-arterial stem cell administration into the affected lower extremity [15-17].