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Human mesenchymal stem cells with enhanced telomerase activity acquire resistance against oxidative stress-induced genomic damage
dc.creator | Trachana V., Petrakis S., Fotiadis Z., Siska E.K., Balis V., Gonos E.S., Kaloyianni M., Koliakos G. | en |
dc.date.accessioned | 2023-01-31T10:09:33Z | |
dc.date.available | 2023-01-31T10:09:33Z | |
dc.date.issued | 2017 | |
dc.identifier | 10.1016/j.jcyt.2017.03.078 | |
dc.identifier.issn | 14653249 | |
dc.identifier.uri | http://hdl.handle.net/11615/79756 | |
dc.description.abstract | Background Human mesenchymal stem cells (MSC) are important tools for several cell-based therapies. However, their use in such therapies requires in vitro expansion during which MSCs quickly reach replicative senescence. Replicative senescence has been linked to macromolecular damage, and especially oxidative stress-induced DNA damage. Recent studies on the other hand, have implicated telomerase in the cellular response to oxidative damage, suggesting that telomerase has a telomere-length independent function that promotes survival. Methods Here, we studied the DNA damage accumulation and repair during in vitro expansion as well as after acute external oxidative exposure of control MSCs and MSCs that overexpress the catalytic subunit of telomerase (hTERT MSCs). Results We showed that hTERT MSCs at high passages have a significant lower percentage of DNA lesions as compared to control cells of the same passages. Additionally, less damage was accumulated due to external oxidative insult in the nuclei of hTERT overexpressing cells as compared to the control cells. Moreover, we demonstrated that oxidative stress leads to diverse nucleus malformations, such as multillobular nuclei or donut-shaped nuclei, in the control cells whereas hTERT MSCs showed significant resistance to the formation of such defects. Finally, hTERT MSCs were found to possess higher activities of the basic antioxidant enzymes, superoxide dismutase and catalase, than control MSCs. Discussion On the basis of these results, we propose that hTERT enhancement confers resistance to genomic damage due to the amelioration of the cell's basic antioxidant machinery. © 2017 International Society for Cellular Therapy | en |
dc.language.iso | en | en |
dc.source | Cytotherapy | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018702013&doi=10.1016%2fj.jcyt.2017.03.078&partnerID=40&md5=23259ff458a7cb7cc1bfa9fa54ddd00c | |
dc.subject | beta1 integrin | en |
dc.subject | catalase | en |
dc.subject | CD34 antigen | en |
dc.subject | endoglin | en |
dc.subject | histone H2AX | en |
dc.subject | superoxide dismutase | en |
dc.subject | telomerase reverse transcriptase | en |
dc.subject | tumor suppressor p53 binding protein 1 | en |
dc.subject | antioxidant | en |
dc.subject | catalase | en |
dc.subject | hydrogen peroxide | en |
dc.subject | superoxide dismutase | en |
dc.subject | telomerase | en |
dc.subject | adipocyte | en |
dc.subject | adipogenesis | en |
dc.subject | adipose tissue | en |
dc.subject | Article | en |
dc.subject | cell differentiation | en |
dc.subject | controlled study | en |
dc.subject | DNA damage | en |
dc.subject | ectopic expression | en |
dc.subject | enzyme active site | en |
dc.subject | enzyme activity | en |
dc.subject | flow cytometry | en |
dc.subject | genomics | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | in vitro study | en |
dc.subject | lung fibroblast | en |
dc.subject | mesenchymal stem cell | en |
dc.subject | micronucleus | en |
dc.subject | molecular weight | en |
dc.subject | osteocyte | en |
dc.subject | oxidative stress | en |
dc.subject | priority journal | en |
dc.subject | telomeric repeat amplification protocol | en |
dc.subject | transposon | en |
dc.subject | cell aging | en |
dc.subject | cell culture | en |
dc.subject | drug effects | en |
dc.subject | genetics | en |
dc.subject | mesenchymal stroma cell | en |
dc.subject | metabolism | en |
dc.subject | physiology | en |
dc.subject | protein subunit | en |
dc.subject | telomere | en |
dc.subject | telomere homeostasis | en |
dc.subject | Antioxidants | en |
dc.subject | Catalase | en |
dc.subject | Cells, Cultured | en |
dc.subject | Cellular Senescence | en |
dc.subject | DNA Damage | en |
dc.subject | Humans | en |
dc.subject | Hydrogen Peroxide | en |
dc.subject | Mesenchymal Stromal Cells | en |
dc.subject | Oxidative Stress | en |
dc.subject | Protein Subunits | en |
dc.subject | Superoxide Dismutase | en |
dc.subject | Telomerase | en |
dc.subject | Telomere | en |
dc.subject | Telomere Homeostasis | en |
dc.subject | Elsevier B.V. | en |
dc.title | Human mesenchymal stem cells with enhanced telomerase activity acquire resistance against oxidative stress-induced genomic damage | en |
dc.type | journalArticle | en |
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