Differential homing and engraftment properties of hematopoietic progenitorcells from murine bone marrow, mobilized peripheral blood, and fetal liver

The rate of reconstitution following hematopoietic stem cell (HSC) transpla ntation differs widely depending on the tissue source of the cells Infused. To test the hypothesis that variability in engraftment kinetics is related to differences In the efficiency with which intravenously transplanted HSC s "home" to the bone marrow (BM), the homing properties of murine fetal liv er (FL), adult BM, and mobilized peripheral blood (MPB) cells were compared . Lethally irradiated mice transplanted with 2 x 10(6) FL, BM, or MPB cells exhibited sequentially slower recovery of circulating leukocytes and plate lets that correlates with the progressively lower frequency of colony-formi ng cells (CFCs) In these tissues. However, differences In the rate and degr ee of early and long-term reconstitution were maintained even after infusin g equal numbers of CFCs derived from FL, BM, and MPB. To compare the homing of progenitors from these tissues, cells were labeled with fluorescent PKH 26 dye and injected into lethally irradiated hosts. Three hours later, PKH2 6(+) cells were reisolated from the BM and spleen by fluorescence-activated cell sorting and assayed for in vitro CFCs. Despite the higher level of ve ry late antigen (VLA)-2, VLA-4, and VLA-5 on Sca1(+)+c-kit(+) cells from FL compared to BM, 10-fold fewer FL CFCs homed to hematopoietic organs than t hose from BM. MPB cells homed slightly better, but still less efficiently t han BM cells. Therefore, clonogenic cells from different tissues exhibit st riking variations in homing efficiency that does not necessarily correlate with engraftment kinetics. Homing is likely counterbalanced by Intrinsic di fferences in proliferative potential that ultimately determine the rate of hematopoietic reconstitution.