In vitro production of megakaryocytes from PIXY321 versus GM-CSF-mobilized peripheral blood progenitor cells.
The generation of megakaryocytes (MK) from cultured peripheral blood progenitor cells (PBSC), harvested via apheresis, from 18 female breast cancer patients treated with either PIXY321 or GM-CSF was compared. Nonadherent mononuclear cells (MNC) were cultured in liquid suspension with 50 U/ml thrombopoietin (TPO) and 2.5% autologous heparinized plasma for 12 days. Flow cytometric analysis was used to measure the percentage of CD34+ on day 1 and CD41+ cells on day 12. The frequency of CD34+ cells was greater in GM-CSF-mobilized samples than in PIXY321-mobilized samples, and MK/MNC yields correlated directly with the number of CD34+ cells seeded, PIXY321-mobilized samples produced more MKs per CD34+ cell than GM-CSF-mobilized samples. Overall, there was no significant difference in the MK/MNC yield between PIXY321- and GM-CSF-mobilized samples. Cyclophosphamide (CY) increased the frequency of CD34+ cells and the corresponding MK/MNC yield for both cytokines, but had no effect on the MK/CD34+ yield. Compared to GM-CSF, PIXY321 mobilization resulted in increased CD34+ cell commitment to the MK lineage.
Lefebvre
P
P
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois, USA.
Winter
J N
JN
Rademaker
A W
AW
Goolsby
C
C
Cohen
I
I
D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor