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Local signals in stem cell-based bone marrow regeneration

机译：基于干细胞的骨髓再生中的局部信号

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摘要

The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.
机译：骨髓（BM）组织发育和再生的细胞基础是通过造血干细胞（HSC）和间充质干细胞（MSC）介导的。造血细胞和BM基质细胞（BMSC）之间的局部相互作用决定了骨髓抑制后造血功能的重建。在这里，我们回顾了在损伤后控制BM再生的BM局部信号。 BMSCs产生的造血生长因子（HGF）和细胞因子是调节BM造血功能的主要因素。对多种物种的早期胚胎发育至关重要的形态发生因子已添加到HSC调节剂家族中，包括Wnt蛋白，Notch配体，BMP和刺猬家族。 HSC和BMSC的全球基因表达分析已开始揭示两种细胞类型的基因的特征标记组。更重要的是，对全球基因表达的分析以及对BM再生过程中局部信号的生化和生物学研究的结合强烈表明，HGF和细胞因子可能不是BM恢复的主要局部调节因子，而是趋化因子（SDF-1，FGF-4）和骨髓抑制后，血管生成生长因子（VEGF-A，Ang-1）在BM重构中起指导作用。 BM再生调节剂的鉴定正在出现管理BM毒性的新方向。

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