Human mesenchymal stem cells with enhanced telomerase activity acquire resistance against oxidative stress-induced genomic damage

Trachana, Varvara; Petrakis, Spyros; Fotiadis, Zisis; Siska, Evangelia K.; Balis, Vasileios; Gonos, Efstathios S.; Kaloyianni, Martha; Koliakos, George

doi:10.1016/j.jcyt.2017.03.078

Cited by 37 publications

(36 citation statements)

References 59 publications

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“…This was also observed by Trachana et al [173] by exposing MSCs overexpressing hTERT to acute oxidative stress. Cells overexpressing hTERT showed lower DNA damage and higher SOD and catalase activity as compared to control cells of the same passages, indicating hTERT as an enhancer of the cellular antioxidant machinery [173].…”

Section: Telomeres: In Vitro Datasupporting

confidence: 77%

“…In accordance to progressive telomere shortening, telomerization of human MSCs through hTERT (human telomerase reverse transcriptase) overexpression allows to bypass the replicative senescence phenotype and to improve in vitro and in vivo functions, while maintaining the cellular phenotype [172]. This was also observed by Trachana et al [173] by exposing MSCs overexpressing hTERT to acute oxidative stress. Cells overexpressing hTERT showed lower DNA damage and higher SOD and catalase activity as compared to control cells of the same passages, indicating hTERT as an enhancer of the cellular antioxidant machinery [173].…”

Section: Telomeres: In Vitro Datamentioning

confidence: 74%

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Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Neri

Borzı̀

2020

Biomolecules

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Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status. The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments.

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Section: Telomeres: In Vitro Datasupporting

confidence: 77%

Section: Telomeres: In Vitro Datamentioning

confidence: 74%

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Neri

Borzı̀

2020

Biomolecules

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“…Recently, this technology has also been applied to alter intracellular ROS levels to maintain stem cell properties in vitro and in vivo. Although oxidative stress can easily induce diverse nuclear malformations, overexpression of TERT in MSCs protects them from nuclear damage and significantly improves the basal activities of antioxidant enzymes, SOD and catalase in MSCs . Knockout of exon 4 of pNO40/PS1D in MSCs results in elevated ROS levels and p16 and Rb expression, consequently accelerating ageing and osteogenic differentiation defects .…”

Section: Strategies To Control Ros Levels For Msc Fates In Vitro and mentioning

confidence: 99%

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Zhao

Peng

et al. 2018

J Cellular Molecular Medi

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Mesenchymal stem cells (MSCs) are broadly used in cell‐based regenerative medicine because of their self‐renewal and multilineage potencies in vitro and in vivo. To ensure sufficient amounts of MSCs for therapeutic purposes, cells are generally cultured in vitro for long‐term expansion or specific terminal differentiation until cell transplantation. Although physiologically up‐regulated reactive oxygen species (ROS) production is essential for maintenance of stem cell activities, abnormally high levels of ROS can harm MSCs both in vitro and in vivo. Overall, additional elucidation of the mechanisms by which physiological and pathological ROS are generated is necessary to better direct MSC fates and improve their therapeutic effects by controlling external ROS levels. In this review, we focus on the currently revealed ROS generation mechanisms and the regulatory routes for controlling their rates of proliferation, survival, senescence, apoptosis, and differentiation. A promising strategy in future regenerative medicine involves regulating ROS generation via various means to augment the therapeutic efficacy of MSCs, thus improving the prognosis of patients with terminal diseases.

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“…These differences can be explained by earlier senescence of adult MSC [17]. Indeed, the telomere length is directly correlated to the age of the donor and to the time of culture before the senescence [18]. Therefore, the use of MSC from Wharton's jelly allows a longer culture than when MSCs come from the BM.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cell Production Compliant with Good Manufacturing Practice: Comparison between Bone Marrow, the Gold Standard Adult Source, and Wharton’s Jelly, an Extraembryonic Source

Laroye

Gauthier

Antonot

et al. 2019

JCM

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Many clinical trials report mesenchymal stem/stromal cells (MSCs) efficacy in various indications. Therefore, standardization of MSC production becomes necessary. MSC properties are impacted by tissue origin, especially if they are from extraembryonic tissue or adult sources. For this reason, we evaluated the impact of MSC tissue origin on production. Methods: Three productions of MSC from Wharton’s Jelly (WJ) or from bone marrow (BM) were performed according to good manufacturing practice. The identity (phenotype, differentiation, and clonogenic capacities), safety (karyotype, telomerase activity, sterility, and donor qualification), and functionality (viability, mixed lymphocyte reaction) of each cell batch were analyzed. Results: Slight differences between MSC sources were observed for phenotype, telomerase activity, and clonogenic capacities. Conclusion: Both sources have made it possible to quickly and easily obtain clinical grade MSC. However, as availability of the source is thought to be essential, WJ seems more advantageous than BM.

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Human mesenchymal stem cells with enhanced telomerase activity acquire resistance against oxidative stress-induced genomic damage

Cited by 37 publications

References 59 publications

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Mesenchymal Stem/Stromal Cell Production Compliant with Good Manufacturing Practice: Comparison between Bone Marrow, the Gold Standard Adult Source, and Wharton’s Jelly, an Extraembryonic Source

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