Direct measurement of local oxygen concentration in the bone marrow of live animals

Article

关键词: HEMATOPOIETIC STEM-CELLS;    MODELING PO(2) DISTRIBUTIONS;    PROGENITOR CELLS;    NICHE;    MICROSCOPY;    PHOSPHORESCENCE;    COMPARTMENT;    GRADIENTS;    TRACKING;    HYPOXIA;   

DOI  :  10.1038/nature13034

来源: SCIE

【 摘 要 】

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(1). Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types(2-4). However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis(5), expression of hypoxia inducible factor-1 alpha (Hif-1 alpha) and related genes(6), and staining with surrogate hypoxic markers (for example, pimonidazole)(6-8). Here we perform direct in vivo measurements of local oxygen tension (p(O2)) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute p(O2) of the bone marrow to be quite low (<32 mm Hg) despite very high vascular density. We further uncovered heterogeneities in local p(O2), with the lowest p(O2) (similar to 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 p(O2) values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.

【 授权许可】

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