Recombinant human ligand for MPL, megakaryocyte growth and development factor (MGDF), stimulates thrombopoiesis in vivo in normal and myelosuppressed baboons

Stem Cells
R G AndrewsP Hunt

Abstract

Megakaryocyte growth and development factor (MGDF) is a ligand for c-mpl and a member of the hematopoietic growth factor superfamily. Recombinant murine MGDF specifically stimulates thrombopoiesis in mice. Recombinant human (rHu) MGDF stimulates megakaryocytic differentiation of baboon CD34+ marrow cells in vitro. Therefore, we determined the in vivo biological effects of rHuMGDF administered to normal baboons in the absence and presence of myelosuppression with 5-fluorouracil (5-FU). rHuMGDF was administered to normal baboons as a single s.c. injection at doses of 1, 10, 25 and 50 micrograms/kg/day for 10 days and, as a control, heat-inactivated MGDF was administered at a dose of 10 micrograms/kg/day. Platelet counts were markedly increased in all animals administered native rHuMGDF but not in animals given heat-inactivated rHuMGDF. Platelet counts began to increase between three and six days after starting rHuMGDF administration and the maximum average increases were 1.7-, 3.4-, 5.1- and 4.0-fold above baseline in animals administered 1, 10, 25 and 50 micrograms/kg/day, respectively. Maximum platelet counts were reached between 7 and 10 days after starting rHuMGDF and maintained for four days after the last dose. Thereafter, ...Continue Reading

References

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Citations

Mar 31, 1999·International Journal of Radiation Oncology, Biology, Physics·M A MouthonG Wagemaker
May 7, 1998·Transfusion Science·L A Harker
May 5, 1999·Current Opinion in Hematology·L A Harker
Feb 5, 2008·Experimental Hematology·Petr BartunekMichal Dvorak
Nov 8, 2006·European Journal of Haematology·Ken-ichi SuzukiTatsutoshi Nakahata
Jan 1, 1998·Hematology·M H Mangi, A C Newland
Sep 15, 1998·Acta Paediatrica. Supplement·J L Nichol

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