Hematopoietic stem cells may be derived from multiple different tissue sources, yet it remains unclear if stem cells from all tissue types are equivalent. Addressing this issue has immediate practical implications for bone marrow transplantation and provides the opportunity to examine fundamental questions in stem cell biology. This proposal seeks to investigate the functional and molecular features of stem cells through comparative studies of human umbilical cord blood and bone marrow in the context of two recently developed in vitro systems: (1) a directed suicide selection technique for enriching quiescent, multipotent stem cells, and (2) an in vitro T-lymphopoiesis model. Through these studies, the molecular phenotype of stem cells, their functional capacity in myeloid development assays and their T-lymphoid differentiation and immunologic repertoire potential will be delineated. Sequential clinical samples after cord blood transplant will permit assessment of how these functional and molecular features of stem cells evolve. Further, correlation of in vitro assay data with clinical outcomes will test the utility of the assays as prognostic indicators for cord blood transplantation.
