The Brain-Bone-Blood Triad: Traffic Lights for Stem-Cell Homing and Mobilization
The Brain-Bone-Blood Triad: Traffic Lights for Stem-Cell Homing and Mobilization
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DOI：
10.1182/asheducation-2010.1.1
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发表时间：
2010-12-01
期刊：
影响因子：
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通讯作者：
Kollet, Orit
中科院分区：
文献类型：
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作者：
Lapidot, Tsvee;Kollet, Orit
将移植的干细胞导航到它们的靶器官对于临床骨髓重建是必不可少的。最近的研究已经确定，造血干细胞（HSC）动态地改变它们的特征和位置，从静止和静止的细胞锚定在骨髓中的循环和运动细胞进入循环。这些变化是由压力信号驱动的。骨髓的双向迁移是形成HSC移植方案基础的主动过程。然而，HSC如何以及为什么进入和退出骨髓作为宿主防御和修复的一部分还没有完全了解。功能性的、临床前的、免疫缺陷的NOD/SCID（非肥胖型糖尿病-严重联合免疫缺陷）小鼠移植模型的开发使得能够表征正常和白血病人类HSC并研究其生物学。深入的研究已经揭示了趋化因子SDF-1（基质细胞衍生因子-1，也称为CXCL 12）在HSC与微环境相互作用中的多个任务，以及控制应激诱导的动员和增强的HSC归巢的重叠机制的存在，主要生理相关的顺序事件。这些过程需要动态相互作用的多系统方面，将骨髓脉管系统和基质细胞与神经和免疫系统联系起来。神经线索作为外部起搏器，通过昼夜节律同步HSC迁移和发育，以平衡骨重塑，从而解决身体生理需求的血液和免疫细胞产生。应激情况和临床HSC动员加速白细胞增殖和骨转换。本文综述了脑-骨-血三联体通过应激信号调控HSC调控骨髓中未成熟和成熟白细胞的概念。
Navigation of transplanted stem cells to their target organs is essential for clinical bone marrow reconstitution. Recent studies have established that hematopoietic stem cells (HSCs) dynamically change their features and location, shifting from quiescent and stationary cells anchored in the bone marrow to cycling and motile cells entering the circulation. These changes are driven by stress signals. Bidirectional migrations to and from the bone marrow are active processes that form the basis for HSC transplantation protocols. However, how and why HSCs enter and exit the bone marrow as part of host defense and repair is not fully understood. The development of functional, preclinical, immune-deficient NOD/SCID (non-obese diabetic-severe combined immunodeficiency) mice transplantation models has enabled the characterization of normal and leukemic human HSCs and investigation of their biology. Intensive research has revealed multiple tasks for the chemokine SDF-1 (stromal cell-derived factor-1, also known as CXCL12) in HSC interactions with the microenvironment, as well as the existence of overlapping mechanisms controlling stress-induced mobilization and enhanced HSC homing, sequential events of major physiological relevance. These processes entail dynamically interacting, multi-system aspects that link the bone marrow vasculature and stromal cells with the nervous and immune systems. Neural cues act as an external pacemaker to synchronize HSC migration and development to balance bone remodeling via circadian rhythms in order to address blood and immune cell production for the physiological needs of the body. Stress situations and clinical HSC mobilization accelerate leukocyte proliferation and bone turnover. This review presents the concept that HSC regulation by the brain-bone-blood triad via stress signals controls the bone marrow reservoir of immature and maturing leukocytes.