Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice

K. Kabaya, K. Shibuya, Y. Torii, Y. Nitta, M. Ida, H. Akahori, T. Kato, M. Kusaka, H. Miyazaki

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15 Citations (Scopus)

Abstract

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 106 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 μg/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 μg/kg/day for 7 days or at an interval of 3 days at 78 μg/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 μg/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.

Original languageEnglish
Pages (from-to)1035-1041
Number of pages7
JournalBone Marrow Transplantation
Volume18
Issue number6
Publication statusPublished - 1996 Dec 1

Keywords

  • Bone marrow transplantation
  • Megakaryocyte
  • Mouse
  • Platelet
  • Thrombopoietin

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Kabaya, K., Shibuya, K., Torii, Y., Nitta, Y., Ida, M., Akahori, H., Kato, T., Kusaka, M., & Miyazaki, H. (1996). Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice. Bone Marrow Transplantation, 18(6), 1035-1041.