"Introduction: Transdifferentiation of umbilical cord (UC) blood, bone marrow (BM) and vessel derived stem cells into endothelial progenitors has been reported both in vitro and in vivo. Encouraging but limited success with these studies suggested the need for identification of more versatile populations of endothelial progenitors or signaling pathways to improve their homing to ischemic sites seeking angiogenesis and neovascularization. Objective: We propose to isolate and characterize in vitro endothelial progenitors derived from BM, placental vessels, and UC blood/matrix and to investigate whether successful in vivo endothelial regeneration, differentiation and maintenance can be achieved by systemic delivery when a defined demand is placed on the endothelium. Next, we propose to investigate whether endothelial progenitors homing to ischemic sites can be enhanced by delivery of chemoatractant molecules into the ischemic bed. Materials and methods: BM, placental vessel, and UC blood/matrix derived stem cell subpopulations will be assessed in clonal growth assays under conditions that promote endothelial commitment, and molecularly characterized for the expression of molecules and genes associated with endothelial lineage. The capacity of these cells to participate in vascular regeneration will be examined following systemic delivery into immunodeficient NOD/SCID mice with experimentally induced cardiac ischemia. Various chemokines will be investigated for their ability to augment endothelial progenitors homing to ischemic sites and to promote endothelial regeneration. Endothelial progenitors contribution to vascular reconstitution will be assessed by histology, immunohistochemistry, electron microscopy and clonal analyses of ischemic tissue samples. Relevance: The proposed study will bring new insights into stem cell research field, advancing the development of cell therapies for vascular regeneration relying on angiogenesis and neovascularization."