Bordeaux University, Bordeaux, France.
Exp Hematol. 2010 Oct;38(10):847-51. doi: 10.1016/j.exphem.2010.06.002. Epub 2010 Jun 12.
Regulation of hematopoiesis depends on cytokines, cellular interactions, transcription, and metabolic factors. Among the latter, O(2) has been neglected for a long time. Recently, an increasing number of publications evidenced the regulatory role of physiological low O(2) concentrations (0.1-5%; similar to those in bone marrow) on the in vitro behavior of hematopoietic stem cells. This brief review utilizes the article of Eliasson and colleagues in this Journal to summarize the major results and questions about the relationships between O(2) and hematopoiesis.
In order to be concise and interesting for readers unfamiliar with this field, we selected only the most significant data that either reinforce or contradict the conclusions of Eliasson et al., but we also provide references of reviews with a more detailed bibliography.
A critical analysis of some key publications provides partial answers to three important questions: is the term hypoxia appropriate to describe physiological low O(2) concentrations? Is a very low O(2) level sufficient to control the quiescence/slow cycling balance of hematopoietic stem cells? Is the O(2) concentration able to modify the effect of cytokines on hematopoietic stem cells?
We propose to use in situ normoxia instead of the confusing term hypoxia when working with normal cells at physiological low O(2) concentrations. We suggest that a very low O(2) concentration is necessary but not sufficient to induce hematopoietic stem cell quiescence. We review some articles showing that O(2) variations modify the effect of cytokines.
造血的调控依赖于细胞因子、细胞间相互作用、转录和代谢因素。在这些因素中,氧气(O2)长期以来一直被忽视。最近,越来越多的出版物证明了生理低氧浓度(0.1-5%;类似于骨髓中的浓度)对体外造血干细胞行为的调节作用。本文利用 Eliasson 及其同事在本刊上的文章,总结了 O2 与造血之间关系的主要结果和问题。
为了简洁明了,让不熟悉该领域的读者感兴趣,我们只选择了最有意义的数据,这些数据要么支持,要么反驳 Eliasson 等人的结论,但我们也提供了更详细参考文献的综述的参考文献。
对一些关键文献的批判性分析为三个重要问题提供了部分答案:用“低氧”一词来描述生理低氧浓度是否合适?非常低的氧水平是否足以控制造血干细胞的静止/缓慢循环平衡?氧浓度能否改变细胞因子对造血干细胞的作用?
我们建议在使用生理低氧浓度的正常细胞时,用原位常氧代替令人困惑的“低氧”一词。我们认为,非常低的氧浓度是诱导造血干细胞静止所必需的,但不是充分的。我们回顾了一些文章,这些文章表明氧变化会改变细胞因子的作用。