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
Abstract
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."
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1996
- Accession Number
- ADA475659
Entities
People
- Ann M. Farese
- Lisa B. Grab
- Pamela Hunt
- Thomas J. Macvittie
Organizations
- Armed Forces Radiobiology Research Institute