Percorrer por autor "Giestinhas, Andrea Alves"
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- MicroRNAs as key regulators of senescence in Mesenchymal Stem CellsPublication . Giestinhas, Andrea Alves; Almeida, Maria Inês; Ferraz, RicardoOsteoarthritis affects over 500 million people worldwide and remains a major health burden. Recent therapeutic approaches involve the intra-articular injection of mesenchymal stem cells (MSCs) to promote cartilage repair and attenuate inflammation. However, large-scale expansion of MSCs for allogeneic therapies is limited by cellular senescence, which arises during repeated in vitro expansion and compromises their proliferative, differentiation, and immunomodulatory capacities. Strategies to modulate senescence are therefore of great interest. MicroRNAs (miRNAs), are potent post-transcriptional regulators of gene expression, representing promising candidates. While several miRNAs are under evaluation in clinical trials for other conditions, their role in MSC senescence remains insufficiently understood. Here, we investigated the miRNA landscape and proteomic profile of senescence in human bone marrow-derived MSCs (hBM-MSCs) exposed to two stressors: γ-irradiation (DNA damage) and H₂O₂ (oxidative stress). Both 10 Gy γ-irradiation and 600 μM H₂O₂ effectively induced senescence, evidenced by reduced proliferation, DNA damage, β-gal activity, and cytoplasmic enlargement. Proteomics analysis identified 61 and 41 differentially expressed proteins under irradiation and H₂O₂, respectively, with 7 shared. Small RNA sequencing revealed 61 miRNAs altered by irradiation and 51 by H₂O₂, with 26 shared. Integrative analysis highlighted conserved families (miR-17, miR-15) and emerging regulators (miR-106b-5p, miR-15b-5p, miR-16-5p), implicating cell-cycle, pluripotency, and stress-response pathways. These findings provide novel insights into miRNA–protein networks governing MSC senescence and suggest potential molecular targets to preserve MSC functionality during expansion.