In vivo effects of pegylated recombinant human megakaryocyte growth and development factor on hematopoiesis in normal mice

被引:32
作者
Kabaya, K [1 ]
Akahori, H [1 ]
Shibuya, K [1 ]
Nitta, Y [1 ]
Ida, M [1 ]
Kusaka, M [1 ]
Kato, T [1 ]
Miyazaki, H [1 ]
机构
[1] KIRIN BREWERY CO LTD,PHARMACEUT RES LAB,TAKASAKI,GUMMA 37012,JAPAN
关键词
megakaryocyte growth and development factor (MGDF); thrombopoietin (TPO); megakaryocytic progenitor; megakaryocyte; platelet;
D O I
10.1002/stem.140651
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The in vivo effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human thrombopoietin modified with polyethylene glycol, were investigated in normal Balb/c mice. PEG-rHuMGDF was more potent in producing platelets and the dose-response curve was steeper compared with the case of the nonpegylated form of this molecule, Five consecutive injections with PEG-rHuMGDF caused a dose-dependent increase in peripheral platelet counts with a peak on day 8. There was a dose-dependent rise in platelet counts on day 8 at daily doses from 0.333 to 30 mu g/kg. Intermediate doses of PEG-rHuMGDF (1.111 to 10 mu g/kg/day) caused a significant decrease in mean platelet volume, and conversely, higher doses of PEG-rHuMGDF (30 to 270 mu g/kg/day) induced a dose-dependent increase in mean platelet volume. There was a dose-dependent decrease in hemoglobin concentration with a minimum on day 8 but no significant reduction in reticulocyte counts following PEG-rHuMGDF administration. White blood cell counts were unchanged by PEG-rHuMGDF treatment. Marrow megakaryocyte size enlarged to 1.5-fold and the number of marrow megakaryocytes increased to sixfold by consecutive administration of PEG-rHuMGDF at 30 mu g/kg/day. A twofold increase in the number of marrow megakaryocytic progenitor cells (colony-forming units-megakaryocyte) was also observed. Marrow erythroid progenitor (colony-forming units-erythroid) counts decreased but splenic colony-forming units-erythroid, marrow and splenic erythro/myeloid progenitor cell counts, and splenic granulocyte/macrophage progenitor cell counts increased with PEG-rHuMGDF treatment. Marrow and splenic erythroid burst-forming cells were unchanged. These results indicate that PEG-rHuMGDF, a truncated molecule of thrombopoietin, is a potent stimulator for megakaryopoiesis and thrombopoiesis, and also affects the development of other hematopoietic cells in normal mice.
引用
收藏
页码:651 / 660
页数:10
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