Direct measurement of local oxygen concentration in the bone marrow of live animals
Open accessAbstract
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.
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In the bone marrow, MSCs reside in low oxygen tension (hypoxia) ranging from 1.5 to 4.2% oxygen depending on location in the marrow space.
“In the bone marrow, MSCs reside in low oxygen tension (hypoxia), which has been shown to range from 1.5 to 4.2% oxygen depending on the location in the marrow space [23].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [23]
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- Authors
- Spencer, J. A., Ferraro, F., Roussakis, E., Klein, A., Wu, J., Runnels, J. M., Zaher, W., Mortensen, L. J., Alt, C., Turcotte, R., Yusuf, R., Côté, D., Vinogradov, S. A., Scadden, D. T., & Lin, C. P.
- Affiliations
- Tufts University (US)
- Harvard University (US)
- Boston University (US)
- Institut Universitaire en Santé Mentale de Québec (CA)
- University of Pennsylvania (US)
- Corresponding author
- Lin, Charles P.
- ORCID
- Venue
- Nature
- Published
- 2014-03-02
- Volume
- 508
- Issue
- 7495
- Pages
- 269-273
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3984353
- OpenAlex
- W2054719244
- Cited by
- 1,167
- References
- 32
- Citations by year
- 2026: 66 · 2025: 64 · 2024: 88 · 2023: 90 · 2022: 106 · 2021: 127 · 2020: 123 · 2019: 110 · 2018: 94 · 2017: 95 · 2016: 79 · 2015: 83 · 2014: 39 · 2012: 1
- FWCI
- 69.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL100402, HL096372, HL097748, R03HL096372, HL097794, R01HL097794, R01HL097748)
- National Institute of Biomedical Imaging and Bioengineering (R01EB014703, EB017274, R01EB017274)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- hypoxia, endosteum, vascular heterogeneity, radiation stress, stem cell quiescence, bone marrow microenvironment
- MeSH terms
- Animals, Hypoxia, Arteries, Bone Marrow, Busulfan, Hematopoietic Stem Cells, Luminescent Measurements, Male, Mice, Inbred C57BL, Microscopy, Oxygen, Cell Hypoxia, Photons, Mice, Stem Cell Niche, Nestin
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