The broad, long-term objective and specific aims of this project are to improve the outcome of patients receiving allogeneic cored blood transplantation through a better understanding of the cord blood cell composition.
The aims are to augment the cord blood graft through complementary strategies such as ex vivo expansion of cord blood cells and combination of selected sub-populations of precursor cells or combined blood units. While the use of cord blood transplantation 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. The major hypothesis we wish to test is whether increased numbers of stem cells (undifferentiated or committed) will result in a more rapid myeloid and lymphoid recovery. Using ex vivo expansion strategies will allow us to determine whether we will be able to expand pluripotent stem cells as well as committed precursors for clinical use. The findings in this project will have an important impact that will lead to further studies in projects I and III. While there are data to suggest that higher numbers of hematopoietic cells results in improved outcome through a more rapid myeloid reconstitution, we are specifically also interested in a more rapid lymphoid recovery. Our preliminary data suggests an important collection between CD34+ cells and CD4+ cell recovery.
Specific aim 1 characterize the cord blood units to determine the overall and specifically lymphoid precursor content.
Specific aim 2 will define and optimize ex vivo expansion conditions.
Specific aim 3 will involve the important clinical studies of the most promising conditions defined.
Specific aim 4 will focus on the pace and extent of clinical immune reconstitution following the cord blood transplantation. These combined studies and the extensive interactions with Project I and III, will allow us to determine whether we are able to improve the clinical outcome for our patients.
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