ArticleStem cells (Dayton, Ohio)2014
miR-335 correlates with senescence/aging in human mesenchymal stem cells and inhibits their therapeutic actions through inhibition of AP-1 activity.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Article
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- Stem cell-derived exosomes: a potential therapeutic strategy for enhancing tendon stem/progenitor cells function in tendon-bone healing.Journal of orthopaedic surgery and research · 2025Review
- Review
- Epigenetic mechanisms in stem cell therapies for achilles tendinopathy.Frontiers in cell and developmental biology · 2025Review
- Suppressing the Aging Phenotype of Mesenchymal Stromal Cells: Are We Ready for Clinical Translation?Biomedicines · 2024Review
- Effects of Replicative Senescence of Human Chorionic MSCs on their EV-miRNA Profile.Stem cell reviews and reports · 2024Article
- miRNAs in the diagnosis and therapy of cardiac and mediastinal tumors: a new dawn for cardio-oncology?Future cardiology · 2024Review
- Mesenchymal Stem Cell Senescence during Aging:From Mechanisms to Rejuvenation Strategies.Aging and disease · 2023Review
- Knockdown of long noncoding RNA SAN rejuvenates aged adipose-derived stem cells via miR-143-3p/ADD3 axis.Stem cell research & therapy · 2023Article
- Aged mesenchymal stem cells and inflammation: from pathology to potential therapeutic strategies.Biology direct · 2023Review
- Antioxidant and phytometabolite profiles of ethanolic extract from the cascara pulp ofF1000Research · 2023Article
- Down-regulation of Jun induces senescence through destabilizing chromatin in osteoarthritis chondrocytes.American journal of translational research · 2023Article
- Senescent cells: A therapeutic target for osteoporosis.Cell proliferation · 2022Review
- The Mechanism of Stem Cell Aging.Stem cell reviews and reports · 2022Review
- miRNAs in Cardiac Myxoma: New Pathologic Findings for Potential Therapeutic Opportunities.International journal of molecular sciences · 2022Review
- Article
- Small Noncoding RNAome Changes During Human Bone Marrow Mesenchymal Stem Cells SenescenceFrontiers in endocrinology · 2022Article
- MiR-217 promotes endothelial cell senescence through the SIRT1/p53 signaling pathway.Journal of molecular histology · 2021Article
- Review
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7 authors.
Funding
Abstract
MicroRNAs, small noncoding RNAs, regulate gene expression primarily at the posttranscriptional level. We previously found that miR-335 is critically involved in the regulation and differentiation capacity of human mesenchymal stem cells (hMSCs) in vitro. In this study, we investigated the significance of miR-335 for the therapeutic potential of hMSCs. Analysis of hMSCs in ex vivo culture demonstrated a significant and progressive increase in miR-335 that is prevented by telomerase. Expression levels of miR-335 were also positively correlated with donor age of hMSCs, and were increased by stimuli that induce cell senescence, such as γ-irradiation and standard O2 concentration. Forced expression of miR-335 resulted in early senescence-like alterations in hMSCs, including: increased SA-β-gal activity and cell size, reduced cell proliferation capacity, augmented levels of p16 protein, and the development of a senescence-associated secretory phenotype. Furthermore, overexpression of miR-335 abolished the in vivo chondro-osseous potential of hMSCs, and disabled their immunomodulatory capacity in a murine experimental model of lethal endotoxemia. These effects were accompanied by a severely reduced capacity for cell migration in response to proinflammatory signals and a marked reduction in Protein Kinase D1 phosphorylation, resulting in a pronounced decrease of AP-1 activity. Our results demonstrate that miR-335 plays a key role in the regulation of reparative activities of hMSCs and suggests that it might be considered a marker for the therapeutic potency of these cells in clinical applications.
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