Synergistic effects of pegylated recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor on mobilization of hematopoietic progenitor and stem cells with long-term repopulating ability into peripheral blood in mice

We investigated the effects of pegylated recombinant human megakaryocyte gr owth and development factor (PEG-rHuMGDF) on peripheral blood progenitor ce ll (PBPC) mobilization and the combined effect of PEG-rHuMGDF plus recombin ant human granulocyte colony-stimulating factor (rhG-CSF) in C57BL/6 mice. Treatment of mice with PEG-rHuMGDF increased the numbers of day 8 and day 1 2 spleen colony-forming units (CFU-S), and pre-CFU-S in the PB. Ten days ad ministration of PEG-rHuMGDF could mobilize higher numbers of days 8 and day 12 CFU-S than 5 days administration. An optimal dose of PEG-rHuMGDF mobili zed a higher number of committed progenitor cells (day 8 CFU-S) and a lower number of immature progenitor cells (pre-CFU-S) into PB than rhG-CSF. The combined administration of optimal or suboptimal doses of PEG-rHuMGDF and r hG-CSF induced synergistic effects on mobilization of CFU-S and pre-CFU-S i nto PB compared to either factor alone. Four months after sex-mismatched PB PC transplantation, long-term donor-derived engraftment was observed in all recipients that had been transplanted with PBPCs mobilized by rhG-CSF and/ or PEG-rHuMGDF, as determined by Y-chromosome polymerase chain reaction (PC R) analysis. Our data suggest that cytokine-induced pathways for PBPC mobil ization may be different between PEG-rHuMGDF and rhG-CSF and indicate that PEG-rHuMGDF alone or the combination with rhG-CSF may be useful in effectiv e PBPC mobilization.