TY - JOUR
T1 - Mobilization of primitive haemopoietic progenitor cells and stem cells with long-term repopulating ability into peripheral blood in mice by pegylated recombinant human megakaryocyte growth and development factor
AU - Torii, Y.
AU - Nitta, Y.
AU - Akahori, H.
AU - Tawara, T.
AU - Kuwaki, T.
AU - Ogami, K.
AU - Kato, T.
AU - Miyazaki, H.
PY - 1998
Y1 - 1998
N2 - We investigated in detail the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on peripheral blood progenitor cell (PBPC) mobilization in male BDF1 mice. Treatment with PEG- rHuMGDF for 5 d stimulated a striking expansion of the circulating levels of multiple types of colony-forming units in culture (CFU-c), including CFU- granulocyte-macrophage, CFU-megakaryocyte, burst-forming units-erythroid, and multipotent CFU-c, and primitive day-12 CFU-spleen. All of these progenitors were mobilized into the peripheral blood (PB) with similar kinetics; their numbers peaked after the cessation of treatment and then declined earlier than platelet numbers peaked. The maximal increase in any of the four CFU-c in the PB was attained with at least 300 μg/kg/d of PEG-rHuMGDF, whereas peripheral platelet counts plateaued at 30 μg/kg/d. Adoptive transfer with PB from PEG- rHuMGDF-treated donor mice resulted in greater survival of lethally irradiated recipients. The majority of the recipients that survived at 187 d after transplantation with PEG-rHuMGDF-mobilized PB showed significant donor engraftment at the progenitor cell level. The combined administration of appropriate doses of PEG-rHuMGDF and recombinant human granulocyte colony-stimulating factor induced a synergistic increase in the circulating levels of the four CFU-c compared to either factor alone. These results indicate that PEG-rHUMGDF as a single agent can mobilize a full spectrum of PBPCs in mice.
AB - We investigated in detail the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on peripheral blood progenitor cell (PBPC) mobilization in male BDF1 mice. Treatment with PEG- rHuMGDF for 5 d stimulated a striking expansion of the circulating levels of multiple types of colony-forming units in culture (CFU-c), including CFU- granulocyte-macrophage, CFU-megakaryocyte, burst-forming units-erythroid, and multipotent CFU-c, and primitive day-12 CFU-spleen. All of these progenitors were mobilized into the peripheral blood (PB) with similar kinetics; their numbers peaked after the cessation of treatment and then declined earlier than platelet numbers peaked. The maximal increase in any of the four CFU-c in the PB was attained with at least 300 μg/kg/d of PEG-rHuMGDF, whereas peripheral platelet counts plateaued at 30 μg/kg/d. Adoptive transfer with PB from PEG- rHuMGDF-treated donor mice resulted in greater survival of lethally irradiated recipients. The majority of the recipients that survived at 187 d after transplantation with PEG-rHuMGDF-mobilized PB showed significant donor engraftment at the progenitor cell level. The combined administration of appropriate doses of PEG-rHuMGDF and recombinant human granulocyte colony-stimulating factor induced a synergistic increase in the circulating levels of the four CFU-c compared to either factor alone. These results indicate that PEG-rHUMGDF as a single agent can mobilize a full spectrum of PBPCs in mice.
KW - Granulocyte colony-stimulating factor
KW - Megakaryocyte growth and development factor
KW - Mobilization
KW - Peripheral blood progenitor cell
KW - Thrombopoietin
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U2 - 10.1046/j.1365-2141.1998.01113.x
DO - 10.1046/j.1365-2141.1998.01113.x
M3 - Article
C2 - 9886338
AN - SCOPUS:0032428366
VL - 103
SP - 1172
EP - 1180
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 4
ER -