Critical Limb Ischemia and Stem Cell Research

Critical limb ischemia (CLI) represents a syndrome that is associated with a particularly adverse natural history. Although clinicians increasingly recognize that peripheral arterial disease (PAD) includes a broad range of clinical syndromes, CLI is associated with very adverse short-term limb and systemic cardiovascular outcomes.1 CLI is not a specific disease per se; rather, it represents a syndrome that may develop from many fundamentally distinct pathophysiological processes, including advanced atherosclerosis, thromboembolism or atheroembolism, in situ thrombosis, and the arteritides, such as thromboangiitis obliterans (TAO, or Buerger disease).Article p 2679 TAO is a form of PAD that is obliterative, thrombotic, and commonly progressive, especially in individuals who sustain exposure to tobacco products.2 Refractory ischemic leg pain, skin ulceration, and gangrene may ensue, with a high short-term risk of amputation. TAO is distinct from other diseases that can obliterate distal arterial beds. It is not adequate to offer a TAO diagnosis to individuals with distal arterial disease who are male and who smoke. Clinicians in practice and investigators should be advised to apply the diagnostic label carefully, such as via use of the Olin criteria.2For most individuals with CLI attributable to atherosclerosis, the immediate therapeutic goal is reestablishment of limb perfusion via endovascular or surgical methods, with aggressive treatment of the causative risk factors. For individuals with TAO, distal arterial obstruction may obviate successful revascularization, and patency may not be easily maintained. Thus, beyond tobacco cessation, there are few therapeutic options that are evidence based and that can sustain real hope for either short- or long-term improvement. Despite past clinical investigation of potential pharmacotherapies, including prostaglandin analogues, vasodilator medications, and other interventions in limited clinical trials, outcomes remain poor.3,4 Because this form of PAD is, by definition, associated with distal arterial obstruction with an associated inflammatory response, …