Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration - PubMed
4 days ago
- #Senescence-targeting vesicles
- #Ferroptosis
- #Intervertebral disc degeneration
- Intervertebral disc degeneration (IDD) is a major cause of spinal disorders, with ferroptosis-induced senescence of nucleus pulposus cells (NPC) playing a critical role.
- Mesenchymal stem cell-derived exosomes (MSC-EVs) were pretreated in a senescent microenvironment to create 'domesticated vesicles' (D-EVs) with enhanced targeting and anti-senescence properties.
- D-EVs are enriched with GPX4 protein and specifically bind to senescent NPCs via the CXCL10-CXCR3 chemokine axis, delivering GPX4 to inhibit ferroptosis and alleviate cellular senescence.
- D-EVs were anchored to a thermosensitive ROS-responsive hydrogel for sustained and on-demand release in the degenerative microenvironment, enhancing their efficacy.
- In vitro and in vivo experiments showed the system significantly suppresses ferroptosis and senescence pathways, preventing NPC senescence phenotype conversion.
- This study presents a novel approach to delay NPC senescence and mitigate IDD progression by inhibiting ferroptosis.