Expansion of hematopoietic stem cells - new possibilities

This review summarizes some of the evidence underlying a hierarchical model of early hematopoietic cell differentiation events in both human and murine systems. It highlights the key features of currently available functional assays (both in vitro and in vivo) for quantitating their most primitive elements. These assays have been used to identify and validate the components of culture media (particularly the types and concentrations of the growth factors added) that influence whether the relevant functional properties of these cells are retained or altered when they are stimulated to proliferate in vitro. Conditions that support modest but consistent expansions of these functionally defined hematopoietic stem cells have already been found. Additionally, conditions that do not alter the survival or proliferative response of these cells, and also do not support the maintenance of their stem cell functions have been discovered. Finally, a new level of complexity in terms of how hematopoietic stem cells are regulated has emerged from analyses of cells from ontologically different sources. These findings help to explain previous difficulties in achieving dramatic in vitro expansions of very primitive hematopoietic cells in spite of early excitement based on studies of clonogenic progenitors.