Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia.
This study compared the therapeutic potential of recombinant, native versus pegylated megakaryocyte growth and development factor (rMGDF and PEG-rMGDF, respectively), as well as that of the combined administration of PEG-rMGDF and r-methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) on hematopoietic reconstitution after 700 cGy, 60Co gamma, total body irradiation in nonhuman primates. After total body irradiation, animals received either rMGDF, PEG-rMGDF, r-metHuG-CSF, PEG-rMGDF and r-metHuG-CSF or HSA. Cytokines in all MGDF protocols were administered for 21-23 d. Either rMGDF, PEG-rMGDF, or PEG-rMGDF and r-metHuG-CSF administration significantly diminished the thrombocytopenic duration (platelet count (PLT) < 20,000 per microliter)to o.25, 0, 0.5 d, respectively, and the severity of the PLT nadir (28,000, 43,000, and 30,000 per microliter, respectively) as compared with the controls (12.2 d duration, nadir 4,000 per microliter), and elicited an earlier PLT recovery. Neutrophil regeneration was augmented in all cytokine protocols and combined PEG-rMGDF and r-metHuG-CSF further decreased the duration of neutropenia compared with r-metHuG-CSF alone. These data demonstrated that the administration of PEG-rMGDF significantly induced bone marrow regeneration versus rMGDF, and when combined with r-metHuG-CSF significantly enhanced multilineage hematopoietic recovery with no evidence of lineage competition.
Farese
A M
AM
Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889, USA.
Hunt
P
P
Grab
L B
LB
MacVittie
T J
TJ
D000818:Animals; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D011833:Radiation Injuries, Experimental / Q000097:blood* / Q000473:pathology / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage; D013926:Thrombopoietin / Q000008:administration & dosage*; D014916:Whole-Body Irradiation
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin