Local signals in stem cell-based bone marrow regeneration
Local signals in stem cell-based bone marrow regeneration
复制标题
基于干细胞的骨髓再生中的局部信号
DOI：
10.1038/sj.cr.7310026
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发表时间：
2006-02-01
期刊：
影响因子：
44.1
通讯作者：
Liu, XY
中科院分区：
文献类型：
--
作者：
Han, W;Yu, Y;Liu, XY
骨髓(BM)组织发育和再生的细胞基础是通过造血干细胞(HSCs)和间充质干细胞(MSCs)介导的。造血细胞和骨髓基质细胞(BMSCs)之间的局部相互作用决定了骨髓抑制后的造血重建。在这里，我们回顾了BM局部信号在侮辱后控制BM再生的作用。骨髓间充质干细胞(BMSCs)产生的造血生长因子(HGFs)和细胞因子是调节骨髓造血的主要因素。在多种物种中对早期胚胎发育至关重要的形态原已被添加到HSCs调节基因家族中，包括Wnt蛋白家族、Notch配体家族、BMPs家族和Hedgehog家族。造血干细胞和骨髓间充质干细胞的全球基因表达分析已经开始揭示这两种细胞类型的标志性基因组。更重要的是，对骨髓再生过程中整体基因表达的分析以及对局部信号的生化和生物学研究有力地表明，HGFs和细胞因子可能不是骨髓恢复的主要局部调节因子，而趋化因子(SDF-1、FGF-4)和血管生成生长因子(VEGF-A、Ang-1)在骨髓抑制后的骨髓重建中起指导作用。BM再生调节剂的鉴定为BM毒性管理提供了一个新的方向。
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.