Recent investigations have highlighted the potential of ex vivo expanded endothelial precursor cells (EPCs) for therapeutic applications in vascular medicine. Bone marrow (BM) or mobilized peripheral blood (mPB) from adults has been primarily used as a stem cell source in these laboratory studies and early clinical trials. The majority of these investigations have involved the infusion of a heterogeneous population of cells, which we hypothesize may result in limited biological effects. This application brings together two complimentary groups with expertise in both the purification and ex vivo expansion (ViaCell) of stem cell populations from umbilical cord blood (UCB) as well as experience in animal models of ischemia (CWRU). UCB is a potentially rich source of angioblasts and presents several advantages to BM and mPB, such as: collection at no risk to the donor, reduced immunogenicity, and lower rates of inherent pathogen transmission. The hypothesis underlying this work is that early endothelial cells (angioblasts or possibly hemangioblasts) are the critical cell population responsible for repair at sites of vascular injury. In this context, purified sub-populations of cells from UCB will be evaluated for their in vitro and in vivo neovascularization potential. Since a higher number of hemangioblasts may improve in vivo reconstitution, as seen with hematopoietic stem cells (HSCs), optimization of ex vivo expansion of hemangioblasts will be applied using the Selective Amplification TM process developed by ViaCell. For this purpose, purified sub-populations of cells derived from CB and their counterparts expanded ex vivo will be assessed in a murine hind limb model of vascular injury to determine whether infused cell populations integrate and function in new vessel formation, and whether this response persists over time. The results of the studies described in this proposal may provide scientific rationale for future clinical applications in patients with ischemic vascular diseases ? ?
