Objective-Peripheral arterial disease (PAD) can have severe consequences on patient mortality and morbidity. In contrast to approaches using growth factor administration or isolated cell transplantation, we attempted to develop an alternative method for ischemic therapy using the transplantation of tissue engineered cell sheets with angiogenic potential. Methods and Results-Human smooth muscle cell (SMC) and fibroblast cell (FbC) sheets were harvested from temperature-responsive culture dishes and transplanted into ischemic hind limbs of athymic rats. ELISA showed significantly increased in vitro secretion of angiogenic factors by SMCs in comparison to FbCs. Twenty-one days after transplantation, laser doppler analysis demonstrated significantly increased blood perfusion in the SMC group. Perfusion with Indian ink and immunohistochemistry also revealed significantly greater numbers of functional capillaries in the SMC group. Finally, cell tracing experiments revealed that some SMCs from the transplanted cell sheets migrated into the ischemic tissues, contributing to newly formed vessels. Conclusions-SMC sheet transplantation allows for controlled and localized delivery of cells that possess angiogenic potential directly to ischemic tissues. Through the secretion of angiogenic factors, as well as cell migration and integration with newly formed vessels, SMC sheet transplantation provides an effective method for the revascularization of ischemic tissues. Key Words: smooth muscle cell Ⅲ cell sheet Ⅲ angiogenesis P eripheral arterial disease (PAD) is the result of obstructed blood flow in the arteries outside of the brain and heart, and in severe cases presents a risk of limb loss. Atherosclerosis is the major pathogenesis of lower extremity peripheral arterial disease (PAD), 1 and patients with PAD have significant overlap with those having coronary artery disease and cerebrovascular disease. 2 Similarly, patients with established atherothrombosis also generally have polyvascular disease throughout the body. 3 Although the cause of death in patients with PAD is not usually attributable to chronic obstructive disease in the peripheral vessels itself, the long-term survival in these patients is greatly reduced because of complications from atherosclerosis. Because of increasing occlusion in other vascular regions, PAD is therefore nevertheless a major cause of morbidity and can lead to a high mortality rate.Therapeutic options for PAD are diverse and variably effective, beginning with lifestyle changes such as weight loss, regular exercise, or cessation of smoking. Pharmacological measures such as antiplatelet medications and hyperbaric oxygen therapy are also mildly effective and generally reserved for minimal disease. 4 For more severe PAD, bypass grafting has become the established method for revascularization to prevent limb loss. However, patency rates as well as a major risk of complications have limited effectiveness, leading to alternative approaches of percutaneous catheterbased interventions. Whereas balloo...