Effects of recombinant human thrombopoietin on megakaryocyte colony formation and megakaryocyte ploidy by human CD34+ cells in a serum-free system.
In serum-free cultures of human CD34 cells, recombinant human thrombopoietin (TPO) induced megakaryocyte colony formation a dose-dependent fashion that was further enhanced by the presence of interleukin-3 (IL-3) and stem cell factor (SCF), but not by IL-6, IL-11 or erythropoietin. TPO gave rise to much smaller colonies and at an earlier time than IL_3, indicating that TPO affects predominantly more mature megakaryocytic progenitors. In liquid cultures. TPO increased the percentage and the absolute number of > or = 8N megakaryocytes, but it did not shift their modal ploidy from 2N. TPO-induced endomitosis was totally inhibited by the presence of or previous exposure of cells to, IL-3 and /or SCF. The mechanism by which TPO overcomes in vivo the negative effects of IL-3 and SCF on megakaryocyte ploidy remains unknown.
Angchaisuksiri
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Hematology/Oncology Section, H.H. McGuire Veterans Affairs Medical Center, Richmond, Virginia 23249, USA.
Carlson
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Dessypris
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D000328:Adult; D018952:Antigens, CD34; D003114:Colony-Forming Units Assay; D016895:Culture Media, Serum-Free; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008533:Megakaryocytes / Q000187:drug effects* / Q000502:physiology; D011003:Ploidies; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*; D013997:Time Factors
D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D013926:Thrombopoietin