Marrow repopu latino potential of selfreplicating non-human primate hematopoiet1c stem cells

Hematopoietic stem cell self-renewal hypotnetically results in the generation of progeny with functional properties similar to the primary stem cell population. Numerous studies indicate, however, that self-renewing stem cells experience either a diminished proliferative capacity leading to replicative senescence or acquire a homing defect which compromises stem cell repopulating potential. Our group has attempted to determine the marrow repopulaling capacity of self-replicating non-human stem cells by monitoring their ability to repopulate myeloablated baboons. An endothelialbased stem cell expansion system was developed and was utilized to promote stem cell self-replication. Self-replicating stem cells were capable of providing cells with both short-term and long-term marrow repopulating potential, The time to engraftment with the self-replicating stem cells was, however, delayed as compared to a primary, purified CD34+ cell graft, although the expanded grafts contained 4-5-fold greater numbers of CD34+ cells. Gene marking studies are currently being carried out to determine the contribution of self-replicating stern cells to both short-term and long-term marrow repopulation. Such studies will better define the consequences of stem cell replication on primary stem cell function. These studies will have important implications to future clinical trials involving stem cell expansion and retroviral-based gene therapy.