Han Wei, Yu Yan, Liu Xin Yuan
Stem Cell Research Center, School of Pharmacy, Shanghai Jiao-Tong University, Shanghai 200030, China.
Cell Res. 2006 Feb;16(2):189-95. doi: 10.1038/sj.cr.7310026.
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.
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。造血细胞与BM基质细胞（BMSCs）之间的局部相互作用决定了骨髓抑制后造血功能的重建。在此，我们综述了损伤后控制BM再生的局部信号。BMSCs产生的造血生长因子（HGFs）和细胞因子是调节BM造血的主要因素。对多种物种早期胚胎发育至关重要的形态发生素已被纳入HSCs调节因子家族，包括Wnt蛋白家族、Notch配体家族、骨形态发生蛋白（BMPs）家族和刺猬蛋白家族。对HSCs和BMSCs的全基因组表达分析已开始揭示这两种细胞类型的特征基因群。更重要的是，对全基因组表达的分析以及BM再生过程中局部信号的生化和生物学研究强烈表明，HGFs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）和血管生成生长因子（VEGF-A、Ang-1）在骨髓抑制后的BM重建中起指导作用。BM毒性管理的一个新方向正从BM再生调节因子的鉴定中显现出来。
