Controlled release of hypoxic exosomes from PLGA microspheres attenuates IVDD progression through activating PPAR-γ and suppressing oxidative stress-mediated NPCs senescence - 04/02/26
, Yingze Zhang a, b, c, f, ⁎ , Di Zhang a, ⁎ Abstract |
Oxidative stress and apoptosis mediated senescence of nucleus pulposus cells (NPCs) and the degradation of extracellular matrix (ECM), which represent a key mechanism underlying intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes hold therapeutic potential for tissue repair; however, their clinical application is limited by rapid clearance, short half-life, and poor target specificity. To overcome these challenges, this study developed poly(lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release carrier for exosomes derived under either normoxic (Exos, 21% O₂) or hypoxic (H-Exos, 1% O₂) conditions. The PLGA microspheres demonstrated high exosome-loading efficiency and provided controlled release for over four weeks. Released hypoxic exosomes activate PPAR-γ pathway, exerting better effects by reducing NPCs SA-β-gal positive rate by 59.8% and elevates Col II and ACAN levels by 30.7% and 25.5%. Animal experiments confirmed that this system effectively attenuated IVDD progression indicating its potential for clinical translation.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Fabricated PLGA microspheres with > 90 % exosome encapsulation efficiency and 4-week controlled release capability. |
• | Hypoxic exosomes significantly enhance the cell activities of NPCs by reducing the SA-β-gal positive rate with 59.8 %. |
• | PLGA@H-Exos antagonize oxidative stress and reduce ROS levels with 61.5 %. |
• | Hypoxic preconditioning enhances the bioactivity of exosomes in activating the PPAR-γ pathway by enriching HIF-1α. |
Keywords : Oxidative stress, Intervertebral disc degeneration, Microspheres, Exosomes, Hypoxia, PPAR-γ pathway
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Vol 195
Article 118940- février 2026 Retour au numéro
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