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

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

Nature (2014-03-05)
Joel A Spencer, Francesca Ferraro, Emmanuel Roussakis, Alyssa Klein, Juwell Wu, Judith M Runnels, Walid Zaher, Luke J Mortensen, Clemens Alt, Raphaël Turcotte, Rushdia Yusuf, Daniel Côté, Sergei A Vinogradov, David T Scadden, Charles P Lin
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 genes, 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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Busulfan, analytical standard, for drug analysis
Busulfan, European Pharmacopoeia (EP) Reference Standard