Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis
Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis
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DOI：
10.1016/j.exphem.2004.06.010
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发表时间：
2004-09-01
影响因子：
2.6
通讯作者：
Goodell, MA
中科院分区：
文献类型：
--
作者：
McKinney-Freeman, S;Goodell, MA
客观的。造血干细胞（HSC）通常存在于骨髓中，但可以在小鼠和人体循环中检测到。据认为，HSC 每天都会进出骨髓，并且返回的 HSC 在表型和功能上通常与其骨髓对应物相同。然而，需要大量的单核血细胞来拯救动物免受致命辐射，这表明循环HSC的患病率较低，或者它们本身就缺乏增殖能力。因此，最近的数据表明，循环 HSC 可能无法在稳态条件下稳定地植入 WBM。本研究的目的是利用联体共生和骨髓移植来详细探索这些动态。材料和方法。对联体共生 CD45 同系小鼠的 WBM 和骨骼肌 HSC 干细胞区室进行了功能分析（通过骨髓移植）和表型分析（通过流式细胞术），以了解联体共生后和手术分离后特定时间点的循环干细胞。结果。令人惊讶的是，我们发现从骨髓贩运进入循环系统的干细胞并不能稳定地返回骨髓，尽管长寿命的淋巴前体细胞确实可以稳定地重新植入。然而，循环中的 HSC 确实驻留在骨骼肌中，其中它们负责 HSC 的活性。结论。循环 HSC 不随骨髓 HSC 流动，并且可以持续存在于外周组织中。 (C) 2004 年国际实验血液学学会。由爱思唯尔公司出版
Objective. Hematopoietic stem cells (HSC), normally resident in bone marrow, can be detected in the murine and human circulation. It is thought that HSC move in and out of bone marrow daily and that returning HSC are generally equivalent to their bone marrow counterparts in phenotype and function. However, large numbers of mononuclear blood cells are required to rescue animals from lethal irradiation, indicating either that the prevalence of circulating HSC is low, or they are inherently deficient in their repopulating ability. Accordingly, recent data suggest that circulating HSC may be unable to stably engraft WBM under homeostatic conditions. The purpose of this study was to explore these dynamics in detail using parabiosis and bone marrow transplantation.Materials and Methods. The WBM and skeletal muscle HSC stem cell compartments of parabiosed CD45 congenic mice were analyzed functionally (via bone marrow transplantation) and phenotypically (via flow cytometry) for circulating stem cells at specific time points postparabiosis and after surgical separation.Results. Surprisingly, we find that stem cells trafficking out of bone marrow and into the circulation do not stably return to bone marrow, although long-lived lymphoid precursors do stably re-engraft. Circulating HSC do, however, take up residence in skeletal muscle, wherein they account for HSC activity.Conclusion. Circulating HSC are not in flux with the bone marrow HSC and can persist in peripheral tissues. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.