Stem Cell Therapy for Vascular Disorders

Abstract

Peripheral vascular disease results from narrowing of the peripheral arteries that supply oxygenated blood and nutrients to the legs and feet. This pathology causes symptoms such as intermittent claudication (pain with walking), painful ischaemic ulcerations, or even limbthreatening gangrene. It is generally believed that the vascular endothelium, a monolayer of endothelial cells (ECs) that lines the luminal surface of all blood and lymphatic vessels, plays a dominant role in vascular homeostasis and vascular regeneration. As a result, stem cell-based regeneration of the endothelium may be a promising approach for the treatment of PAD. Critical limb ischaemia (CLI) is an advanced form of peripheral artery disease which is responsible for about 100,000 amputations each year in the US. Trials to date have reported clinical improvement and reduced need for amputation in patients with CLI who receive autologous bone marrow or mobilised peripheral blood stem cells for stimulation of angiogenesis. There is no effective treatment for lower limb ischaemia caused by peripheral vascular disease and it is necessary to amputate the limb at the end stage. Therefore, the concept of effective therapeutic angiogenesis has become widely accepted during the past few years and it has emerged as a strategy to treat tissue ischaemia by promoting collateral growth using drug, gene or cell therapy. This article provides an overview of current therapeutic challenges for the treatment of critical limb ischaemia, the basic mechanisms of stem cell therapy, the most relevant clinical trials as well as future directions for translational research in this area.