This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Presently, there are no clinically effective methods to enhance arterial perfusion for patients with severe peripheral vascular disease (PVD). Endothelial progenitor cells (EPCs) expressing the surface antigens CD34, CD133 and VEGFR-2 have recently been discovered in the mononuclear cell fraction of bone marrow and peripheral blood. EPCs have been shown to participate in angiogenesis and vascular remodeling in preclinical studies and in a clinical trial in Japan. The purpose of this study, a phase I, FDA- and IRB-approved clinical trial, is to determine if intramuscular injection of autologous bone marrow mononuclear cells (MNCs) containing progenitor cell populations induces an angiogenic response in patients with limb threatening ischemia without any significant adverse events. Initially, ten patients will be recruited to determine safety. Safety of the therapy will be monitored by a Data Safety Monitoring Board and determined by a risk-benefit analysis. If the procedure is determined to be safe, ten additional patients will be recruited to determine efficacy of treatment using objective measures of arterial perfusion of the treated leg. Primary measures of perfusion will be arteriography and ankle- brachial pressure recording. Secondary measures of perfusion will include MRI, assessment of rest pain, transcutaneous oxygen measurements and wound healing. The purpose of this proposal is to determine if stem cell mediated angiogenesis is a safe and effective means of increasing blood flow in the legs of patients with vascular disease. Furthermore, the information gained from this study will be critical in the design of future cell-based therapies for cardiovascular disease.
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