Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells
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Background: Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. Results: After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G 1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Conclusion: Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.
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Some studies reported conflicting results showing negative or no effects on MSCs by hypoxia.
“Yet, some studies reported conflicting results showing negative or no effects on MSCs by hypoxia [34–36].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [34]
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- Authors
- Holzwarth, C., Vaegler, M., Gieseke, F., Pfister, S. M., Handgretinger, R., Kerst, G., & Müller, I.
- Affiliations
- University Children's Hospital Tübingen (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Müller, Ingo
- Venue
- BMC Cell Biology
- Published
- 2010-01-28
- Volume
- 11
- Issue
- 1
- Pages
- 11-11
- ISSN
- 1471-2121 (ISSN-L)
- PMC
- PMC2827377
- OpenAlex
- W2057597564
- Cited by
- 314
- References
- 45
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 11 · 2023: 11 · 2022: 16 · 2021: 19 · 2020: 21 · 2019: 21 · 2018: 19 · 2017: 22 · 2016: 33 · 2015: 28 · 2014: 26 · 2013: 26 · 2012: 20
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Cell Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- José Carreras Leukämie-Stiftung
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- mesenchymal stem cells, hypoxia, oxygen partial pressure, HIF-1α, cell proliferation, cell cycle, adipogenesis, osteogenic differentiation, chromosome stability, immunophenotype, hematopoietic niche, bone marrow, cellular plasticity, platelet lysate
- MeSH terms
- Adolescent, Bone Marrow Cells, Cell Differentiation, Child, Child, Preschool, Female, Humans, Infant, Male, Cell Hypoxia, Immunophenotyping, G1 Phase, Stromal Cells, Multipotent Stem Cells, Chromosomal Instability, Cell Proliferation, Hypoxia-Inducible Factor 1, alpha Subunit, Mesenchymal Stem Cells
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