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.

摘要

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 colonystimulating 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-metHuGCSF, PEG-rMGDF and r-metHuG-CSF, or HSA. Cytokines in all MGDF protocols were administered daily for 18 d, HSA and r- metHuG-CSF alone 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/ml' to 0.25, 0, and 0.5 d, respectively, and the severity of the PLT nadir '28,000, 43,000, and 30,000/ ml, respectively' as compared with the controls '12.2 d duration, nadir 4, 000/ml', 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 PEGrMGDF 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. 'J. Clin. Invest. 1996. 97:2145-2151.'.