Megakaryocyte growth and development factor stimulates enhanced platelet recovery in mice after bone marrow transplantation.
Megakaryocyte growth and development factor (MGDF) is a recently characterized ligand for the cell surface receptor mpl. We have evaluated the effects of polyethylene glycollated recombinant human MGDF (PEG-rHuMGDF) on recovery of hematopoietic cells in mice following bone marrow transplantation (BMT) to support lethal irradiation. Mice treated with PEG-rHuMGDF (50 micrograms/kg/d) had accelerated recovery of platelet numbers compared with BMT mice treated with carrier or recombinant human granulocyte colony-stimulating factor (rHuG-CSF, 72 or 200 micrograms/kg/d). In contrast, PEG-rHuMGDF had no effect on white blood cell (WBC) or red blood cell (RBC) recovery. As previously reported, animals treated with rHuG-CSF had an enhanced recovery of WBC but not platelet or RBC levels. Interestingly, BMT receipient mice treated with the combination of PEG-rHuMGDF and rHuG-CSF showed simultaneous enhanced recovery of both leukocytes and platelets. PEGylated rHuMGDF was found to be considerably more potent than non-PEGylated rHuMGDF in this setting. PEG-rHuMGDF is an effective growth factor for enhancing platelet recovery in mice following BMT either alone or in combination with rHuG-CSF. It will be of interest to evaluate in a clinical setting the ratios of PEG-rHuMGDF and rHuG-CSF for simultaneous administration of these factors and accelerated recovery of both leukocytes and platelets.
Molineux
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G
Amgen Center, Thousand Oaks, CA 91320, USA.
Hartley
C A
CA
McElroy
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P
McCrea
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C
McNiece
I K
IK
D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000473:pathology*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D058851:GPI-Linked Proteins; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology*; D008562:Membrane Glycoproteins; D000090204:Mesothelin; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins; D011092:Polyethylene Glycols; D011506:Proteins / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D011828:Radiation Chimera; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D013926:Thrombopoietin / Q000494:pharmacology* / Q000502:physiology
D003115:Colony-Stimulating Factors; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D016179:Granulocyte Colony-Stimulating Factor; C082218:MPL protein, human; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D000090204:Mesothelin