Effects of Hypoxia on Megakaryocyte Progenitors Obtained from the Umbilical Cord Blood of Term and Preterm Neonates
Publisher:
Karger
E-ISSN:
1661-7819|89|2|104-108
ISSN:
1661-7800
Source:
Neonatology,
Vol.89,
Iss.2, 2006-02,
pp. : 104-108
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Abstract
Background: Placental insufficiency is associated with early-onset thrombocytopenia in preterm neonates. Prior studies demonstrated a reduction in circulating megakaryocyte (Mk) progenitors, suggesting decreased platelet production. We hypothesized that decreased Mk production is the result of a direct inhibitory effect of hypoxia on the proliferation of Mk progenitors, or a hypoxia-induced change in the fetal hematopoietic environment. Objective: To test the effects of hypoxia on the clonogenic maturation of Mk progenitors obtained from term and preterm cord blood CD34pos cells, either cultured alone or in conjunction with CD34neg light density mononuclear cells (LDMCs). Methods: CD34pos cells and CD34neg LDMCs were isolated from the cord blood of term and preterm deliveries, and mobilized peripheral blood CD34pos cells were obtained from healthy adults. CD34pos cells were then cultured alone or co-cultured with CD34neg LDMCs in a semisolid, serum-free media containing rTpo, IL-3, and IL-6. Cultures were exposed to 20%, 5%, or 1% oxygen for 10–12 days. Mk colonies were then quantified following immunohistochemical staining. Results: Pure CD34pos cells from preterm (n = 5) and term (n = 5) neonates and from adults (n = 4) generated similar numbers of Mk colonies in all three oxygen concentrations. However, the number of Mk colonies in preterm co-cultures was progressively lower with decreasing O2 concentrations. Conclusions: Hypoxia did not appear to directly inhibit colony formation of Mk progenitors from preterm and term cord blood CD34pos cells. However, co-culture studies showed a decrease in Mk colony formation with hypoxia, suggesting an indirect inhibitory effect of hypoxia on Mk clonogenic maturation mediated by non-progenitor cells in the hematopoietic microenvironment.