Year 4

Our group works on developing methods for successful transplantatioon of blood stem cells to treat fetuses with genetic disorders such as sickle cell disease or thalassemia. In this grant, we are using novel stem cells that will differentiate into blood-forming cells and other techniques to improve the engraftment of these cells. Our strategies involve using antibodies to deplete stem cell from the fetal host to create “space” in the bone marrow for the engraftment of the newly transplanted cells. A second strategy involves co¬≠ transplanting regulatory T cells,which may prevent an immune response against the transplanted cells. In this reporting period, we have made progress inimplementing a strategy that involves harvesting bone marrow cells from the mother and transplanting large numbers of these cells, along with Tcells to promote engraftment. into the fetus in a large animal model. We have determined that this strategy is safe and feasible. Experiments to determine levels of engraftment and the differentiation profiles of the en.grafted cells are under way.