Leukocyte Biology Section, NHLI Division, Faculty of Medicine, Imperial College London, UK.
Immunol Lett. 2012 Jul 30;145(1-2):47-54. doi: 10.1016/j.imlet.2012.04.009.
The adult bone contains a number of distinct populations of stem cells, including haematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells and fibrocytes. While haematopoietic stem cells are required to provide a lifelong supply of blood cells it is thought that the other populations of stem cells play a role in tissue regeneration and potentially disease. The chemokine CXCL12 is produced constitutively in the bone marrow and, acting via CXCR4, is critical in maintaining HSPCs in a quiescent state and retaining all subsets of stem and progenitor cells in the bone marrow environment. The cytokine G-CSF, used clinically to mobilize haematopoietic stem cells for bone marrow transplants, activates the sympathetic nervous system and bone marrow macrophages to reduce the expression of CXCL12 by bone marrow stromal cells, thereby promoting the exit of haematopoietic stem cells from the bone marrow. Understanding the molecular mechanisms underlying G-CSF stimulated mobilization has led to development of CXCR4 antagonists as fast acting mobilizing agents for haematopoietic stem cells. Evidence now suggests that CXCR4 antagonists can similarly mobilize distinct subsets of progenitor cells, namely the endothelial progenitor cells and mesenchymal stem cells, but this requires conditioning of the bone marrow with VEGF rather than G-CSF.
成人骨骼中包含许多不同的干细胞群体，包括造血干细胞、间充质干细胞、内皮祖细胞和成纤维细胞。虽然造血干细胞是提供终生供应血细胞所必需的，但其他干细胞群体被认为在组织再生和潜在疾病中发挥作用。趋化因子 CXCL12 在骨髓中持续产生，并通过 CXCR4 发挥作用，对于维持 HSPCs 的静止状态以及将所有干细胞和祖细胞亚群保留在骨髓环境中至关重要。细胞因子 G-CSF 临床上用于动员造血干细胞进行骨髓移植，它激活交感神经系统和骨髓巨噬细胞，减少骨髓基质细胞表达 CXCL12，从而促进造血干细胞从骨髓中退出。对 G-CSF 刺激动员背后的分子机制的理解导致了 CXCR4 拮抗剂的开发，作为造血干细胞的快速动员剂。现在有证据表明，CXCR4 拮抗剂也可以类似地动员不同的祖细胞亚群，即内皮祖细胞和成纤维细胞，但这需要使用 VEGF 而不是 G-CSF 对骨髓进行预处理。
