It is the broad, long-term goal of this program to improve the outcome of patients undergoing cord blood transplantation (CBT). While the use of CBT has resulted in improved outcome in selected patients, there remains a significant amount of work that needs to be done to improve on the outcome for all patients. Two areas that need immediate improvement are those of engraftment and immune reconstitution. To this end, the investigators of this application will utilize the approach of translational research, bridging the novel experimental concepts and observations made at the laboratory bench to clinical application at the patients' bedside. The major hypothesis we wish to test is whether increased numbers of stem cells (undifferentiated and/or committed) will result in a more rapid myeloid and lymphoid recovery. There are three projects proposed. Project I will focus on the pre clinical studies of engraftment and immune reconstitution utilizing in vitro and a murine model of CBT. Project II will study the key areas of regulation of T cells by the thymus and the contribution of the thymus to the recovery following CBT. Project III will encompass the clinical studies for this application attempting to increase the numbers of stem ells through expansion or addition of other sources of stem cells. Each of these projects is highly interactive. These projects are supported by two cores (administration and biostatistics/data management). One of the remarkable interactions of this program is the interactions from the bench to the bedside but of equal importance from the bedside to the bench. This ability of interact with clinicians and laboratory investigators in a bi-directional way will provide the greatest input for potential benefit for patients. This program project will focus on the use and understanding of cord blood cells used in allogeneic transplantation with specific detailed to cell dose required for myeloid and lymphoid engraftment and the immune competence of the cells following this procedure with specific emphasis on the role of the thymus.
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