QUANTITATIVE AND CELL-CYCLE DIFFERENCES IN PROGENITOR CELLS MOBILIZEDBY RECOMBINANT HUMAN INTERLEUKIN-7 AND RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR

Administration of recombinant human interleukin-7 (rhIL-7) to mice inc reases the exportation of myeloid progenitors (colony-forming unit [CF U]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM] ) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in t he peripheral blood (PB). We now report that combined treatment of mic e with rhIL-7 and recombinant human granulocyte-colony stimulating fac tor (rhG-CSF) stimulates a twofold to 10-fold increase in the total nu mber of PB CFU-c, and a twofold to fivefold increase in the total numb er of PB CFU-spleen at day 8 (CFU-S-8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhI L-7 or rhG-CSF alone. These differences in mobilizing efficiency sugge st qualitative differences in the mechanisms by which rhIL-7 and rhG-C SF mobilize progenitor cells. In fact, the functional status of progen itor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenito rs obtained from the PB is about 20-fold higher for rhIL-7-treated mic e than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and trac king studies, and highlight different functions and rates of repopulat ion after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF.