HOMING AND TRAFFICKING OF HEMATOPOIETIC PROGENITOR CELLS

Investigations of the homing of transplanted hemopoietic cells into pr econditioned recipients have in most studies been referable to paramet ers that determine engraftment. The principles, however, that govern t heir early traffic into the host's blood and tissues have remained muc h less explored. Early studies and experiments from our own laboratory suggest that intravenously administered hemopoietic cells, including progenitors, are not selectively taken up by bone marrow, as they are distributed widely in several tissues (liver, lung, kidney, spleen, bo ne marrow). As the hemopoietic cells are later on found almost exclusi vely in the bone marrow (and spleen in the mouse), the data argue for either preferential retention in these tissues or just only preferenti al survival and proliferation. Our recent studies showing modulation o f cells lodged to the bone marrow, before proliferation ensues (i.e. 3 h after infusion), would favor preferential retainment and/or surviva l of these cells within the bone marrow. Furthermore we established th at the VLA(4)/VCAM-1 adhesion pathway plays a significant role in this process, thus defining VCAM-1 as the dominant bone marrow endothelial addressin in hemopoietic cell homing. Since homing likely represents a cascade of adhesive interactions between hemopoietic cells and bone marrow stroma and/or its extracellular matrix, other adhesion pathways are likely to be involved and remain to be defined. Finally, our data on mobilization of hemopoietic progenitors from normal individuals, i nduced by blocking the VLA(4)/VCAM-1 adhesion pathway, suggest that th e molecular pathways involved in homing are also of importance in gove rning hemopoietic progenitor cell trafficking in and out of the bone m arrow.