In Situ Normoxia Enhances Survival and Proliferation Rate of Human Adipose Tissue-Derived Stromal Cells without Increasing the Risk of Tumourigenesis
Open accessAbstract
Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.
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A large number of studies demonstrated that MSCs cultured in hypoxia exhibit higher rates of proliferation and better retain their stem cell properties.
“A large number of studies demonstrated that MSCs cultured in hypoxia exhibit higher rates of proliferation and better retain their stem cell properties [25, 30–33].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [31]
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Cited by
Sorted by citations
Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells
Antebi, B., Rodriguez, L. A., Walker, K. P., Asher, A. M., Kamucheka, R. M., Alvarado, L., Mohammadipoor, A., & Cancio, L. C. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-1007-x · Cited by 137 · see citing works
- Authors
- Choi, J. R., Pingguan-Murphy, B., Wan Abas, W. A. B., Yong, K. W., Poon, C. T., Noor Azmi, M. A., Omar, S. Z., Chua, K. H., Xu, F., & Wan Safwani, W. K. Z.
- Affiliations
- University of Malaya (MY)
- National University of Malaysia (MY)
- Xi'an Jiaotong University (CN)
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-01-23
- Volume
- 10
- Issue
- 1
- Pages
- e0115034
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4304807
- OpenAlex
- W2040318031
- Cited by
- 63
- References
- 77
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 12 · 2017: 5 · 2016: 5 · 2015: 4
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The University of Malaya Research Repository (University of Malaya) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Greater South Information System
- Funders
- National Natural Science Foundation of China (111 Project, 11120101002, 11372243, B06024)
- Universiti Malaya (UM.C/HIR/MOHE/ENG/44)
- Higher Education Discipline Innovation Project (B06024)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- adipose tissue-derived stromal cells, low oxygen tension, tumourigenesis, cell proliferation, cell survival, DNA damage, vascular endothelial growth factor, basic fibroblast growth factor, tumor suppressor, telomere length, telomerase activity, cell expansion
- MeSH terms
- Adipose Tissue, Adult, Cells, Cultured, Female, Humans, Oxygen, Cell Hypoxia, Telomerase, Tumor Suppressor Proteins, Vascular Endothelial Growth Factor A, Cell Proliferation, Telomere Homeostasis, Mesenchymal Stem Cells, Carcinogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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