Dose-response relationship of megakaryocyte progenitors from the bone marrow of thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin.
Megakaryocyte (MK) progenitors from the marrow of adults undergo dose-dependent clonogenic proliferation in response to recombinant thrombopoietin (rTpo). It is unknown whether progenitors from the marrow of thrombocytopenic neonates display rTpo dose-dependent proliferation and whether they are more or less sensitive to rTpo than progenitors from non-thrombocytopenic neonates or adults. To assess this, we cultured marrow from four thrombocytopenic and four non-thrombocytopenic neonates, and from six healthy adults, in a serum-free system in the presence of increasing concentrations of rTpo (0-100 ng/ml). Marrow from the thrombocytopenic and non-thrombocytopenic neonates generated three times more MK colonies/105 light density cells (129 +/- 39 and 167 +/- 30 respectively) than marrow from adults (54 +/- 30, P < 0.0001) at a rTpo concentration of 50 ng/ml. Neonatal and adult samples had a rTpo dose-dependent increase in MK colonies. However, neonates reached a maximal number of colonies at a rTpo concentration of 10 ng/ml, compared with 50 ng/ml in adults, resulting in a larger area under the rTpo dose-response curve for neonatal progenitors (P = 0. 0047). Neonates also generated more large MK colonies than the adults (24% vs. 2% at 100 ng/ml).
Sola
M C
MC
Division of Neonatology, Department of Paediatrics, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA. Solamc@peds.ufl.edu
Du
Y
Y
Hutson
A D
AD
Christensen
R D
RD
D000328:Adult; D019540:Area Under Curve; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008533:Megakaryocytes / Q000187:drug effects* / Q000473:pathology; D013921:Thrombocytopenia / Q000628:therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*
D013926:Thrombopoietin