Barbier Valérie, Winkler Ingrid G, Lévesque Jean-Pierre
Mater Medical Research Institute, Aubigny Place, Raymond Terrace, South Brisbane, QLD, Australia.
Methods Mol Biol. 2012;904:117-38. doi: 10.1007/978-1-61779-943-3_11.
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.
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药物扰乱HSC龛的细胞成分的能力，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的产生。尽管动员治疗抑制龛细胞的机制仍未完全明确，但最近发现骨髓巨噬细胞在维持成骨细胞、骨形成以及HSC维持所必需的CXCL12、KIT配体和血管生成素-1的表达方面起着关键作用。在本章中，我们描述了如何通过用氯膦酸盐负载的脂质体耗尽巨噬细胞来将小鼠HSC动员到血液中，并将这种动员方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。文中还举例详细描述了分析表型和功能重建HSC动员的具体方法。
