Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes.
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.
Pastos
Karen M
KM
Shands Cancer Center, University of Florida, Gainesville, FL, USA.
Slayton
William B
WB
Rimsza
Lisa M
LM
Young
Linda
L
Sola-Visner
Martha C
MC
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*
D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D013926:Thrombopoietin