Nature2014-06-19 2:34 PM

活骨髓中的氧压测定 Direct measurement of local oxygen concentration in the bone marrow of live animals


论文摘要 

低氧压(缺氧)被普遍认为是很多干细胞类型维持静止状态的一个共同特征。然而,低氧浓度(比如说在骨髓中)此前却从未被直接测到过。现在,Charles Lin及同事建立一个基于双光子显微镜的方法,来测定活动物骨髓中的绝对局部氧压(pO2)。采用这一方法,他们发现:虽然血管密度在整个骨髓中是高的,但整体氧合(oxygenation)水平却非常低,局部pO2就血管类型和位置而言有所不同。例如,出人意料的是,骨内膜区域并不是pO2最低的区域。在放疗或化疗之后,骨髓pO2水平升高,而且移植的造血干细胞/祖细胞并不会寻找pO2最低的区域而前往之。

Abstract 

Characterization of how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for the therapeutic manipulation of stem cells. Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types. However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis, expression of hypoxia inducible factor-1α (Hif-1α) and related genes6, and staining with surrogate hypoxic markers (for example, pimonidazole). Here we perform direct in vivo measurements of local oxygen tension (pO2) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute pO2 of the bone marrow to be quite low (<32 mm Hg) despite very high vascular density. We further uncovered heterogeneities in local pO2, with the lowest pO2 (~9.9 mm Hg, or 1.3%) found in deeper peri-sinusoidal regions. The endosteal region, by contrast, is less hypoxic as it is perfused with small arteries that are often positive for the marker nestin. These pO2 values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.

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