Oxidative Stress Mediates Depot-Specific Functional Differences of Human Adipose-Derived Stem Cells
Open accessAbstract
BACKGROUND: Visceral (VS) fat depot is known to have defective adipogenic functions compared to subcutaneous (SC) fat, but its mechanism of origin is unclear. OBJECTIVE: We tested our hypothesis that the degree of oxidative stress in adipose-derived stem cells (ASCs) from these depots may account for this difference. METHODS: ASCs were isolated from VS (omental region) and SC (abdominal region) fat depots of human subjects undergoing bariatric surgery. ASCs from VS and SC fat were investigated for their cellular characteristics in reactive oxygen species (ROS), metabolism, gene expression, proliferation, senescence, migration, and adipocyte differentiation. ASCs were also treated with antioxidant ascorbic acid (vitamin C). RESULTS: We found that human VS-derived ASCs exhibit excessive oxidative stress characterized by high reactive oxygen species (ROS), compared to SC-derived ASCs. Gene expression analyses indicate that the VS-ASCs exhibit higher levels of genes involved in pro-oxidant and pro-inflammatory pathways and lower levels of genes in antioxidant and anti-inflammatory pathways. VS-ASCs have impaired cellular functions compared to SC-ASCs, such as slower proliferation, early senescence, less migratory activity, and poor adipogenic capability in vitro. Treatment with ascorbic acid decreased ROS levels drastically in VS-ASCs. Ascorbic acid treatment substantially improved proliferation, senescence, migration, and adipogenic capacities of compromised ASCs caused by high ROS. CONCLUSIONS: This finding suggests the fat depot-specific differences of cellular defects originating from stem cell population. Considering clinical potentials of human ASCs for cell therapies, this also offers a possible strategy for improving their therapeutic qualities through antioxidants.
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Increased oxidative stress is a major driver of senescence.
“Increased oxidative stress (OS) is a further major driver of senescence [16,17,18,19,20,21].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [21]
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- Authors
- Sriram, S., Yuan, C., Chakraborty, S., Tay, W., Park, M., Shabbir, A., Toh, S.-A., Han, W., & Sugii, S.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Duke-NUS Medical School (SG)
- National University Hospital (SG)
- National University of Singapore (SG)
- Corresponding author
- Sugii, Shigeki
- Venue
- Stem Cell Research & Therapy
- Published
- 2019-05-21
- Volume
- 10
- Issue
- 1
- Pages
- 141-141
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC6528291
- OpenAlex
- W2947461116
- Cited by
- 27
- References
- 22
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 1
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- A*STAR BMRC
- Singapore-China Joint Grant Project (#1412424003)
- A*STAR Joint Council Office (DPG #1334k00083)
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- adipose-derived stem cells, oxidative stress, visceral fat, subcutaneous adipose tissue, reactive oxygen species, adipogenesis, cellular senescence, cell proliferation, cell migration, vitamin C, antioxidants, inflammation, bariatric surgery, cell therapy
- MeSH terms
- Cell Movement, Humans, Inflammation, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress, Gene Expression Regulation, Developmental, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Bariatric Surgery, Subcutaneous Fat, Intra-Abdominal Fat, Mesenchymal Stem Cells
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