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 Blood, 15 November 2006, Vol. 108, No. 10, pp. 3360-3362.
Prepublished online as a Blood First Edition Paper on August 3, 2006; DOI 10.1182/blood-2006-04-018036.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Brief report

Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes

Karen M. Pastos, William B. Slayton, Lisa M. Rimsza, Linda Young, and Martha C. Sola-Visner

From the Shands Cancer Center, University of Florida, Gainesville, FL; the Department of Pediatrics, University of Florida, Gainesville, FL; the Department of Biostatistics, University of Florida, Gainesville, FL; and the Department of Pathology, University of Arizona, Tucson, AZ.

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.


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