Sola M C, Du Y, Hutson A D, Christensen R D
Division of Neonatology, Department of Paediatrics, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA.
Br J Haematol. 2000 Aug;110(2):449-53. doi: 10.1046/j.1365-2141.2000.02163.x.
Megakaryocyte (MK) progenitors from the marrow of adults undergo dose-dependent clonogenic proliferation in response to recombinant thrombopoietin (rTpo). It is unknown whether progenitors from the marrow of thrombocytopenic neonates display rTpo dose-dependent proliferation and whether they are more or less sensitive to rTpo than progenitors from non-thrombocytopenic neonates or adults. To assess this, we cultured marrow from four thrombocytopenic and four non-thrombocytopenic neonates, and from six healthy adults, in a serum-free system in the presence of increasing concentrations of rTpo (0-100 ng/ml). Marrow from the thrombocytopenic and non-thrombocytopenic neonates generated three times more MK colonies/105 light density cells (129 +/- 39 and 167 +/- 30 respectively) than marrow from adults (54 +/- 30, P < 0.0001) at a rTpo concentration of 50 ng/ml. Neonatal and adult samples had a rTpo dose-dependent increase in MK colonies. However, neonates reached a maximal number of colonies at a rTpo concentration of 10 ng/ml, compared with 50 ng/ml in adults, resulting in a larger area under the rTpo dose-response curve for neonatal progenitors (P = 0. 0047). Neonates also generated more large MK colonies than the adults (24% vs. 2% at 100 ng/ml).
来自成年个体骨髓的巨核细胞（MK）祖细胞会对重组血小板生成素（rTpo）产生剂量依赖性的克隆增殖反应。目前尚不清楚血小板减少新生儿骨髓中的祖细胞是否表现出rTpo剂量依赖性增殖，以及它们对rTpo的敏感性是否高于或低于非血小板减少新生儿或成年个体的祖细胞。为了评估这一点，我们在无血清系统中，在rTpo浓度不断增加（0 - 100 ng/ml）的情况下，培养了4名血小板减少新生儿、4名非血小板减少新生儿以及6名健康成年人的骨髓。在rTpo浓度为50 ng/ml时，血小板减少和非血小板减少新生儿的骨髓产生的MK集落数/105低密度细胞比成年人骨髓多三倍（分别为129±39和167±30，而成年人为54±30，P < 0.0001）。新生儿和成年人的样本中，MK集落数随rTpo剂量增加。然而，新生儿在rTpo浓度为10 ng/ml时达到集落数最大值，而成年人在50 ng/ml时达到最大值，这导致新生儿祖细胞的rTpo剂量反应曲线下面积更大（P = 0.0047）。新生儿产生的大型MK集落也比成年人多（在100 ng/ml时分别为24%和2%）。
