Stem cells of the lower limb: their role and potential in management of critical limb ischemia

Peripheral arterial occlusive disease (PAOD) contributes to decreased exercise tolerance, poor balance, impaired proprioception, muscle atrophy and weakness, with advanced cases resulting in critical limb ischemia (CLI) where the viability of the limb is threatened. Patients with a diagnosis of CLI have a poor life expectancy due to concomitant cardio and cerebrovascular diseases. The current treatment options to avoid major amputation by re-establishing a blood supply to the limb generally have poor outcomes. Human skeletal muscle contains both multipotent stem cells and progenitor cells and thus has a capacity for regeneration. Phase I and II studies involving transplantation of bone marrow-derived progenitor cells into CLI limbs show positive effects on wound healing and angiogenesis; the increase in quiescent satellite cell numbers observed in CLI muscle may also provide a sufficient in vivo source of resident stem cells. These indigenous cells have been shown to be capable of forming multiple mesodermal cell lineages aiding the repair and regeneration of chronically ischemic muscle. They may also serve as a repository for autologous transplantation. The behavior and responses of the stem cell population in CLI is poorly understood and this review tries to elucidate the potential of these cells and their future role in the management of CLI.