DESCRIPTION (provided by applicant):  The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive PAD include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients, for many of whom amputation represents the only hope for alleviation of symptoms. The ultimate failure of medical treatment and mechanical revascularization in significant numbers of patients has led to attempts to develop alternative therapies for ischemic disease. These strategies include administration of angiogenic cytokines, either as recombinant protein or as gene therapy, and more recently, to investigations of cell therapy. The concept that new blood vessel formation could be augmented by administering bone marrow cells or circulating endothelial progenitor cells (EPCs) is based upon work performed in our laboratory and others in the past 7 years. The purpose of this pilot clinical protocol is to investigate the efficacy and safety of intramuscular injection of autologously derived EPCs in patients with PAD as a means of augmenting blood vessel formation and perfusion. The rationale for this human protocol is based upon preclinical studies performed in our laboratory and detailed in this application. The completion of the proposed studies will provide data regarding the safety and efficacy of EPC therapy necessary for the design of larger randomized trials and will also provide valuable insights regarding treatment of ischemic disease with a cell based approach.