Clinical application of stem cells for therapeutic angiogenesis in patients with peripheral arterial disease.

Peripheral arterial disease (PAD) may ultimately cause to the loss of the affected limb due to gangrene or infection. Some patients with PAD may have severe coexisting diseases and diffuse involvement of their distal arteries, and so they are poor candidates for revascularization procedures. Angiogenesis has recently been suggested to be a new emerging treatment strategy for patients with PAD. Angiogenesis is defined as the sprouting of new capillaries from pre-existing vascular structures; this process plays a major role in the development of collateral vessels in an ischemic limb. Yet, the exact mechanism of angiogenesis is currently poorly understood. It has been established that angiogenesis is initiated by hypoxia and it requires various pro-angiogenic factors such as vascular endothelial growth factor. Therapeutic angiogenesis is aimed at enhancing natural angiogenesis by the administration of the cells or genes that can trigger angiogenesis and this can lead to pain relief and wound healing by the development of collateral vessels. Most of the recent clinical trials have reported that stem cell therapy for promoting angiogenesis in patients with PAD improves the ischemic symptoms and enhances wound healing. However, there are several limitations to approve a standard treatment for PAD such as small sample size in several prevous studies, their diverse inclusion criteria and the lack of standard assessment methods for the safety and outcome. Therefore, multicenter, large-scale and randomized controlled studies are needed to prove the safety and efficacy of the clinically applying stem cells for therapeutic angiogenesis in patients with PAD.