Human mesenchymal stem cells with enhanced telomerase activity acquire resistance against oxidative stress-induced genomic damage
| Autor: | Zisis Fotiadis, Spyros Petrakis, Martha Kaloyianni, Varvara Trachana, Vasileios Balis, George Koliakos, Efstathios S. Gonos, Evangelia K. Siska |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Senescence Cancer Research Telomerase DNA damage Immunology medicine.disease_cause Antioxidants Superoxide dismutase 03 medical and health sciences 0302 clinical medicine medicine Humans Immunology and Allergy Telomerase reverse transcriptase Cells Cultured Cellular Senescence Genetics (clinical) Transplantation biology Superoxide Dismutase Mesenchymal stem cell Telomere Homeostasis Mesenchymal Stem Cells Hydrogen Peroxide Cell Biology Telomere Catalase Molecular biology Cell biology Oxidative Stress Protein Subunits 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Oxidative stress DNA Damage |
| Zdroj: | Cytotherapy. 19:808-820 |
| ISSN: | 1465-3249 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect