Full reconstitution of human platelets in humanized mice after macrophage depletion
Full reconstitution of human platelets in humanized mice after macrophage depletion
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DOI：
10.1182/blood-2012-01-407890
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发表时间：
2012-08-23
期刊：
影响因子：
20.3
通讯作者：
Yang, Yong-Guang
中科院分区：
文献类型：
--
作者：
Hu, Zheng;Yang, Yong-Guang
人胎胸腺组织和CD 34（+）胎肝细胞在非肥胖糖尿病（NOD）/严重联合免疫缺陷（SCID）或NOD/SCID/γ c（-/-）小鼠体内共移植可导致多系人造血细胞的发育。在这项研究中，我们表明这些人源化小鼠的人类血小板水平极低。人巨核细胞在骨髓中以正常浓度存在表明，人巨核细胞分化在这些小鼠中有效发生。巨噬细胞耗竭后，血液中人血小板迅速增加至与人外周血单核细胞（PBMC）相当的水平，表明小鼠巨噬细胞是人源化小鼠中人血小板重建不良的原因。为了支持这种可能性，人血小板在输注到未处理的小鼠中后迅速被排斥，但在巨噬细胞耗尽的小鼠中持续存在。这些发现表明，抑制或消除受体小鼠巨噬细胞可能提供了一个有用的手段，在体内使用免疫缺陷小鼠评估人类血小板生成和血小板功能。（血。2012;120（8）：1713-1716）
Cotransplantation of human fetal thymic tissue and CD34(+) fetal liver cells in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) or NOD/SCID/gamma c(-/-) mice results in the development of multilineage human hematopoietic cells. In this study, we show that these humanized mice had extremely low levels of human platelets. The presence of human megakaryocytes at a normal concentration in the bone marrow suggests that human megakaryocytic differentiation occurred efficiently in these mice. Rapid increase in human platelets in blood to levels comparable with those of human peripheral blood mononuclear cells (PBMCs) after macrophage depletion indicates that mouse macrophages are responsible for the poor human platelet reconstitution in humanized mice. In support of this possibility, human platelets were rapidly rejected after infusion into untreated mice, but persisted in macrophage-depleted mice. These findings indicate that inhibition or depletion of recipient mouse macrophages may provide a useful means for evaluating human thrombopoiesis and platelet function in vivo using immunodeficient mice. (Blood. 2012;120(8):1713-1716)