Oxidative Stress in Mesenchymal Stem Cell Senescence: Regulation by Coding and Noncoding RNAs

Rosa Vono*, Eva Jover Garcia, Gaia Spinetti, Paolo Madeddu

*Corresponding author for this work

Research output: Contribution to journalReview article (Academic Journal)

20 Citations (Scopus)
263 Downloads (Pure)

Abstract

Significance: Mesenchymal stem cells (MSCs), adult stem cells with the potential of differentiation into mesodermal lineages, play an important role in tissue homeostasis and regeneration. In different organs, a subpopulation of MSCs is located near the vasculature and possibly represents the original source of lineage-committed mesenchymal progenitors. Recent Advances: The plasticity and immune characteristics of MSCs render them a preferential tool for regenerative cell therapy. Critical Issues: The culture expansion needed before MSC transplantation is associated with cellular senescence. Moreover, accelerated senescence of the total and perivascular MSC pool has been observed in humans and mouse models of premature aging disorders. MSC dysfunction is acknowledged as a culprit for the aging-associated degeneration of mesodermal tissues, but the underlying epigenetic pathways remain elusive. This article reviews current understanding of mechanisms impinging on MSC health, including oxidative stress, Nrf2-antioxidant responsive element activity, sirtuins, noncoding RNAs, and PKCs. Future Directions: We provide evidence that epigenetic profiling of MSCs is utilitarian to the prediction of therapeutic outcomes. In addition, strategies that target oxidative stress-associated mechanisms represent promising approaches to counteract the detrimental effect of age and senescence in MSCs. - Antioxid. Redox Signal. 29, 864-879.

Original languageEnglish
Article numberARS-2017-7294-ver9-Vono_1P
Pages (from-to)864-879
Number of pages16
JournalAntioxidants and Redox Signaling
Volume29
Issue number9
Early online date11 Sep 2017
DOIs
Publication statusPublished - 20 Sep 2018

Keywords

  • Cell Therapy
  • Mesenchymal Stem Cells
  • Pericytes
  • Reactive Oxygen Species
  • Senescence

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