title: In vitro production of megakaryocytes from PIXY321 versus GM-CSF-mobilized peripheral blood progenitor cells.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lefebvre
authors.forename: J N
authors.initials: JN
authors.lastname: Winter
authors.forename: A W
authors.initials: AW
authors.lastname: Rademaker
authors.forename: C
authors.initials: C
authors.lastname: Goolsby
authors.forename: I
authors.initials: I
authors.lastname: Cohen
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor