The specific objectives of this contract are (1) To characterize the phenotypes of the common hematopoietic/stromal stem cell (CSC) and human hematopoietic stem cell (HSC) from adult bone marrow, fetal bone marrow, cord blood and mobilized peripheral blood; (2) to further purify both stem cells with the goal of increasing the frequency of expanding FACS sorted single CSC and HSC in culture. The single cell cultures will be used to screen for substances that increase the capacity of store stem cells to """"""""self-renew"""""""" and grow without differentiation; (3) to characterize the murine counterpart of the common hematopoietic/stromal stem cell (mCSC), and to determine a pre- transplant conditioning regime that will allow the successful growth of these cells and their progeny in allogeneic recipients; (4) to develop a chimeric human-mouse model system in which the growth of the human hematopoietic microenvironment is created; (5) to determine a pre-transplant and post-transplant conditioning regime that will allow the growth of the CSC and their progeny in syngeneic recipients; and (6) to determine the utility of the mouse-human chimeras in studying the vivo growth of hHSC and hCSC.
