The DOI matches its Crossref record; 95 of the 95 references it cites were found in a registry or an index.
Human Bone Marrow-Derived Mesenchymal Stem Cells Display Enhanced Clonogenicity but Impaired Differentiation With Hypoxic Preconditioning
Open accessAbstract
Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multilineage differentiative capabilities after prolonged ex vivo propagation. We investigated the use of hypoxia as a preconditioning agent and in differentiating cultures to enhance MSC function. Culture in 5% ambient O2 consistently enhanced clonogenic potential of primary MSCs from all donors tested. We determined that enhanced clonogenicity was attributable to increased proliferation, increased vascular endothelial growth factor secretion, and increased matrix turnover. Hypoxia did not impact the incidence of cell death. Application of hypoxia to osteogenic cultures resulted in enhanced total mineral deposition, although this effect was detected only in MSCs preconditioned in normoxic conditions. Osteogenesis-associated genes were upregulated in hypoxia, and alkaline phosphatase activity was enhanced. Adipogenic differentiation was inhibited by exposure to hypoxia during differentiation. Chondrogenesis in three-dimensional pellet cultures was inhibited by preconditioning with hypoxia. However, in cultures expanded under normoxia, hypoxia applied during subsequent pellet culture enhanced chondrogenesis. Whereas hypoxic preconditioning appears to be an excellent way to expand a highly clonogenic progenitor pool, our findings suggest that it may blunt the differentiation potential of MSCs, compromising their utility for regenerative tissue engineering. Exposure to hypoxia during differentiation (post-normoxic expansion), however, appears to result in a greater quantity of functional osteoblasts and chondrocytes and ultimately a larger quantity of high-quality differentiated tissue.
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“Thus, the question whether hypoxia preconditioning should become the standard of care for clinical application of MSCs remains to be answered [37, 38].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [38]
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Metadata
- Authors
- Boyette, L. B., Creasey, O. A., Guzik, L., Lozito, T., & Tuan, R. S.
- Affiliations
- National Institutes of Health (US)
- University of Pittsburgh (US)
- Corresponding author
- Tuan, Rocky S.
- Venue
- Stem Cells Translational Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01-16
- Volume
- 3
- Issue
- 2
- Pages
- 241-254
- ISSN
- 2157-6564 (ISSN-L)
- 2157-6580
- PMC
- PMC3925051
- OpenAlex
- W1985367412
- Cited by
- 121
- References
- 95
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5 · 2023: 12 · 2022: 14 · 2021: 7 · 2020: 8 · 2019: 10 · 2018: 13 · 2017: 10 · 2016: 15 · 2015: 9 · 2014: 4
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells Translational Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z01AR41131)
- Commonwealth of Pennsylvania Department of Health (SAP4100050913)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, bone marrow-derived stem cells, hypoxic preconditioning, clonogenicity, osteogenic differentiation, adipogenesis, chondrogenesis, vascular endothelial growth factor, alkaline phosphatase, extracellular matrix turnover, stem cell expansion, regenerative medicine
- MeSH terms
- Hypoxia, Cell Differentiation, Cells, Cultured, Clone Cells, Fibroblasts, Humans, Osteocytes, Oxygen, Immunophenotyping, Cytokines, Cell Death, Adipocytes, Ischemic Preconditioning, Chondrocytes, Matrix Metalloproteinases, Cell Proliferation, Mesenchymal Stem Cells
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