Mobilization of bone marrow-derived cells enhances the angiogenic response to hypoxia without transdifferentiation into endothelial cells
Mobilization of bone marrow-derived cells enhances the angiogenic response to hypoxia without transdifferentiation into endothelial cells
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DOI：
10.1161/01.res.0000189259.69645.25
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发表时间：
2005-11-11
影响因子：
20.1
通讯作者：
Skalak, TC
中科院分区：
文献类型：
--
作者：
O'Neill, TJ;Wamhoff, BR;Skalak, TC
骨髓源性细胞（BMCs）通过直接转分化为内皮细胞（ECs）或间接释放生长因子而被认为是血管生长的调节剂。为了在生理条件下研究这些可能性，我们开发了一种小鼠脊髓肌肉中缺氧介导的血管生成模型。这允许整体贴装分析;因此，可以沿着分化标记物观察血管网络内BMC的形态和位置。我们将骨髓移植嵌合小鼠暴露于缺氧环境中，并用粒细胞巨噬细胞集落刺激因子治疗一个亚群。暴露于缺氧导致毛细血管密度相对于对照增加13%。缺氧并没有增加肌肉驻留BMC的总数，但确实增加了25%的圆形BMC的数量。尽管一些BMC呈现毛细血管周围的周细胞形态，但对内皮细胞没有明显的BMC贡献。粒细胞巨噬细胞集落刺激因子治疗进一步增加了肌肉内圆形BMC的数量，并导致血管生成增加23%。这项研究的结果表明，通过旁分泌释放的生长因子，但不转分化成内皮细胞在缺氧过程中的BMCs的潜在的有益作用。
Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis in the mouse spinotrapezius muscle. This allows whole-mount analysis; therefore, the morphology and location of BMCs within the vascular network may be observed along with differentiation markers. We exposed bone marrow transplant chimeric mice to hypoxia and treated a subset with granulocyte macrophage colony-stimulating factor. Exposure to hypoxia caused an 13% increase in capillary density relative to control. Hypoxia did not increase the overall number of muscle-resident BMCs, but did increase the number of rounded BMCs by 25%. There was no discernable BMC contribution to the endothelium, although some BMCs assumed a pericyte morphology around capillaries. Granulocyte macrophage colony-stimulating factor treatment further increased the number of round BMCs within the muscle and caused a 23% increase in angiogenesis. The results of this study suggest a potentially beneficial action of BMCs during hypoxia through paracrine release of growth factors but not transdifferentiation into ECs.