Extrinsic control of stem cell fate: practical considerations

Decades of experimental data suggest that hematopoietic stem cells can remain quiescent, divide, differentiate or die and further, that these cell fate decisions are determined by extracellular signals provided by the hematopoietic microenvironment (ME). Given the importance of the ME for regulating hematopoiesis, it is imperative that transplanted stem cells migrate efficiently and home to appropriate niches where they can receive regulatory signals. Currently the rapid engraftment seen after transplantation of cytokine-mobilized blood-derived stem cells would suggest that these cells are well-equipped for homing. More recent concerns have now been raised by the possibility that in vitro expansion of these stem cells may diminish their ability to engraft. One possible explanation for this is that expansion protocols may alter adhesion molecule expression and consequently homing. Data presented in this report indicate that expression of adhesion molecules is altered following in vitro exposure to recombinant cytokines, and that various combinations of cytokines differentially modulate adhesion molecule expression.