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Distinct bone marrow blood vessels differentially regulate hematopoiesis

机译:不同的骨髓血管差异调节造血作用

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摘要

Bone marrow (BM) endothelial cells (BMECs) form a network of blood vessels (BVs) which regulate both leukocyte trafficking and hematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles and if these events occur at the same vascular site. We found that BM stem cell maintenance and leukocyte trafficking are regulated by distinct BV types with different permeability properties. Less permeable arterial BVs maintain HSCs in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the BM. A functional consequence of high BVs permeability is that exposure to blood plasma increases BM HSPC ROS levels, augmenting their migration capacity while compromising their long term repopulation and survival potential. These findings may have relevance for clinical hematopoietic stem cell transplantation and mobilization protocols.
机译:骨髓(BM)内皮细胞(BMEC)形成了一个血管网络(BV),可调节白细胞运输和造血干祖细胞(HSPC)的维持。但是,尚不清楚BMEC如何平衡这些双重作用以及这些事件是否发生在同一血管部位。我们发现,BM干细胞的维持和白细胞的运输受到具有不同渗透性的BV类型的调节。渗透性较低的动脉BV将HSC维持在低活性氧(ROS)状态,而渗透性较高的正弦曲线促进HSPC活化,并且是未成熟和成熟的白细胞往返于BM的唯一位置。高BV渗透性的功能性后果是,暴露于血浆会增加BM HSPC ROS水平,从而增加其迁移能力,同时损害其长期种群和生存潜力。这些发现可能与临床造血干细胞移植和动员方案有关。

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