Submitted January 3, 2006
Accepted July 10, 2006
Differential effects of recombinant thrombopoietin and
bone marrow stromal conditioned media on neonatal vs.
adult megakaryocytes
Karen M Pastos, William B Slayton, Lisa M Rimsza, Linda Young, and Martha C Sola-Visner*
Shands Cancer Center and the Departments, University of Florida, FL, USA
Department of Pediatrics, University of Florida, FL, USA
Department of Pathology, University of Arizona, Tucson, AZ, USA
Department of Biostatistics, University of Florida, FL, USA
* Corresponding author; email: martha.sola-visner{at}drexelmed.edu.
Umbilical cord blood (CB) is a valuable source of stem
cells for transplantation, but CB transplants 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- vs. 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 biological responses to Tpo and potentially to other cytokines.
