Mobilization of hematopoietic stem cells by depleting bone marrow macrophages.

Mobilization of hematopoietic stem cells by depleting bone marrow macrophages.
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DOI:
10.1007/978-1-61779-943-3_11
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发表时间:
2012-01-01
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
通讯作者:
Levesque, Jean-Pierre
Levesque, Jean-Pierre
中科院分区:
其他
文献类型:
--
作者:
Barbier, Valerie;Winkler, Ingrid G;Levesque, Jean-Pierre

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促进造血干细胞 (HSC) 动员的一个重要因素是动员细胞因子和化疗扰乱 HSC 微环境的细胞成分(特别是成骨细胞及其祖细胞)并抑制 HSC 支持性细胞因子和趋化因子产生的能力。尽管动员治疗抑制微环境细胞的机制尚不完全清楚,但最近发现骨髓巨噬细胞在维持成骨细胞、骨形成以及 HSC 维持所需的 CXCL12、KIT 配体和血管生成素-1 的表达方面发挥着关键作用。在本章中,我们描述了如何通过负载氯膦酸盐的脂质体消耗巨噬细胞来动员 HSC 进入小鼠血液,并将这种动员模式与粒细胞集落刺激因子和环磷酰胺诱导的动员进行比较。通过示例描述了分析表型和功能重建 HSC 动员的详细方法。
An important factor contributing to hematopoietic stem cell (HSC) mobilization is the ability of mobilizing cytokines and chemotherapy to disturb the cellular components of HSC niches, particularly osteoblasts and their progenitors, and to inhibit the production of HSC supportive cytokines and chemokines. Although the mechanisms by which niche cells are inhibited by mobilizing treatments is still incompletely understood, it has recently emerged that bone marrow macrophages play a critical role in maintaining osteoblasts, bone formation, and the expression of CXCL12, KIT ligand, and angiopoietin-1 necessary to HSC maintenance. In this chapter, we describe how to mobilize HSC into the blood in mice by depleting macrophages with clodronate-loaded liposomes and compare this mode of mobilization to mobilization induced by granulocyte colony-stimulating factor and cyclophosphamide. Detailed methods to analyze mobilization of phenotypic and functional reconstituting HSC are described with examples.