Selenium Supplementation Restores the Antioxidative Capacity and Prevents Cell Damage in Bone Marrow Stromal Cells In Vitro
Abstract
Bone marrow stromal cells (BMSCs) and other cell populations derived from mesenchymal precursors are developed for cell-based therapeutic strategies and undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS) of cellular and environmental origin are involved in redox signaling, cumulative cell damage, senescence, and tumor development. Selenium-dependent (glutathione peroxidases [GPxs] and thioredoxin reductases [TrxRs]) and selenium-independent (superoxide dismutases [SODs] and catalase [CAT]) enzyme systems regulate cellular ROS steady state levels. SODs process superoxide anion to hydrogen peroxide, which is subsequently neutralized by GPx and CAT; TrxR neutralizes other ROS, such as peroxinitrite. Primary BMSCs and telomerase-immortalized human mesenchymal stem cells (hMSC-TERT) express GPx1-3, TrxR1, TrxR2, SOD1, SOD2, and CAT. We show here that in standard cell cultures (5%-10% fetal calf serum, 5-10 nM selenite), the activity of antioxidative selenoenzymes is impaired in hMSC-TERT and BMSCs. Under these conditions, the superoxide anion processing enzyme SOD1 is not sufficiently stimulated by an ROS load. Resulting oxidative stress favors generation of micronuclei in BMSCs. Supplementation of selenite (100 nM) restores basal GPx and TrxR activity, rescues basal and ROS-stimulated SOD1 mRNA expression and activity, and reduces ROS accumulation in hMSC-TERT and micronuclei generation in BMSCs. In conclusion, BMSCs in routine cell culture have low antioxidative capacity and are subjected to oxidative stress, as indicated by the generation of micronuclei. Selenite supplementation of BMSC cultures appears to be an important countermeasure to restore their antioxidative capacity and to reduce cell damage in the context of tissue engineering and transplantation procedures.
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In vitro, selenium supplementation reduces ROS levels, DNA damage, telomere shortening, and senescence biomarkers in bone marrow stromal cells, cultured human fibroblasts, and keratinocytes.
“For instance, in bone marrow stromal cells [443], cultured human fibroblasts [412], and keratinocytes [413], Se supplementation reduces ROS levels, DNA damage, telomere shortening and senescence biomarkers.”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [443]
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- Authors
- Ebert, R., Ulmer, M., Zeck, S., Meissner‐Weigl, J., Schneider, D., Stopper, H., Schupp, N., Kassem, M., & Jakob, F.
- Affiliations
- University of Würzburg (DE)
- Musculoskeletal Research Center, Orthopaedic Department, University of Würzburg, Würzburg, Germany
- Odense University Hospital (DK)
- Corresponding author
- Jakob, Franz
- ORCID
- Venue
- STEM CELLS
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-05
- Volume
- 24
- Issue
- 5
- Pages
- 1226-1235
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2117378607
- Cited by
- 200
- References
- 72
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 12 · 2022: 9 · 2021: 7 · 2020: 13 · 2019: 9 · 2018: 14 · 2017: 9 · 2016: 9 · 2015: 13 · 2014: 11 · 2013: 19 · 2012: 12
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- selenium supplementation, selenite, mesenchymal stem cells, oxidative stress, reactive oxygen species, antioxidant enzymes, glutathione peroxidase, thioredoxin reductase, superoxide dismutase, catalase, micronuclei, cell culture conditions, telomerase-immortalized cells, cell damage
- MeSH terms
- Base Sequence, Bone Marrow Cells, Cells, Cultured, Culture Media, DNA Damage, Humans, Molecular Sequence Data, Oxidoreductases, RNA, Selenium, Micronucleus Tests, Stromal Cells, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, Cell Proliferation, Mesenchymal Stem Cells
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