Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice.
We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is capable of improving thrombocytopenia and promoting thrombopoietic reconstitution following lethal irradiation and bone marrow transplantation (BMT) in mice. Immediately after receiving 10 Gy whole body irradiation (day 0), male C3H/HeN mice were inoculated with 10(6) bone marrow cells obtained from syngeneic mice. Circulating platelet counts decreased to below 4% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28 in the control mice undergoing BMT. Subcutaneous consecutive treatment with PEG-rHuMGDF at doses from 10 to 300 micrograms/kg/day from day 1 for 13 days significantly improved the platelet nadir and promoted platelet recovery. The white blood cell counts and hemoglobin concentration following BMT were not influenced by the PEG-rHuMGDF. PEG-rHuMGDF-injection starting from day 5 did not improve the platelet nadir following BMT. Furthermore, administration with PEG-rHuMGDF on alternate days at 55.7 micrograms/kg/day for 7 days or at an interval of 3 days at 78 micrograms/kg/day for 4 days (twice a week for 2 weeks) had a significant efficacy, but these administration regimens had less efficacy than consecutive administration at 30 micrograms/kg/day for 13 days. The numbers of megakaryocytes and megakaryocyte progenitor cells decreased to 5 and 0.2% of normal level, respectively, in the control mice. Consecutive administration of PEG-rHuMGDF enhanced the recovery of the mean number of these cells compared to those in vehicle-treated mice, although such effects were not statistically significant except for the number of megakaryocyte progenitors on day 12. These results suggest that consecutive treatment with PEG-rHuMGDF beginning from the day after BMT may be effective in improving thrombocytopenia following BMT.
Kabaya
K
K
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki, Gunma, Japan.
Shibuya
K
K
Torii
Y
Y
Nitta
Y
Y
Ida
M
M
Akahori
H
H
Kato
T
T
Kusaka
M
M
Miyazaki
H
H
D000818:Animals; D016026:Bone Marrow Transplantation; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000209:etiology; D013926:Thrombopoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000009:adverse effects; D014916:Whole-Body Irradiation / Q000009:adverse effects
D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin