Therapeutic angiogenesis for peripheral artery disease: stem cell therapy

Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis that is associated with a significant limitation in limb function due to ischaemia and high risk of cardiovascular mortality. The lower limb manifestations of PAD principally fall into the categories of chronic stable claudication, critical leg ischaemia, and, rarely, acute limb ischaemia. Lower limb ischaemia induced by PAD is a major health problem. In the absence of effective pharmacological, interventional or surgical treatment, amputation is undertaken at the end-stage as a solution to unbearable symptoms. The concept of "therapeutic angiogenesis" has become widely accepted during the past few years. Bone marrow consists of multiple cell populations, including endothelial progenitor cells, which have been shown to differentiate into endothelial cells and release several angiogenic factors and thereby enhance neovascularisation in animal models of hind limb ischaemia. The promising results from various preclinical studies provide the basis for clinical trials using bone marrow-derived cells or non-bone marrow cells, like cells from the peripheral blood or other tissues. However, the mechanisms by which these cells exert their positive effects are poorly understood until now. This review summarises the data from experimental and clinical studies related to peripheral arterial disease and cellular therapy.