title: Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes.
abstract: Umbilical cord blood (CB) is a valuable source of stem cells for transplantation, but CB transplantations are frequently complicated by delayed platelet engraftment. The reasons underlying this are unclear. We hypothesized that CB- and peripheral-blood (PB)-derived megakaryocytes (MKs) respond differently to the adult hematopoietic microenvironment and to thrombopoietin (Tpo). To test this, we cultured CB- and PB-CD34(+) cells in adult bone marrow stromal conditioned media (CM) or unconditioned media (UCM) with increasing concentrations of recombinant Tpo and compared the effects of these conditions on CB-versus PB-MKs. PB-MKs reached highest ploidy in response to UCM + 100 ng/mL rTpo, and the addition of CM inhibited their maturation. In contrast, CB-MKs reached highest ploidy in CM without rTpo, and high rTpo concentrations (> 0.1 ng/mL) inhibited their maturation. This is the first evidence that human neonatal and adult MKs have substantially different biologic responses to Tpo and potentially to other cytokines.
authors.affiliation: Shands Cancer Center, University of Florida, Gainesville, FL, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Pastos
authors.forename: William B
authors.initials: WB
authors.lastname: Slayton
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Linda
authors.initials: L
authors.lastname: Young
authors.forename: Martha C
authors.initials: MC
authors.lastname: Sola-Visner
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins; D017154:Stromal Cells / Q000378:metabolism*; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D013926:Thrombopoietin