ArticleBioactive materials2026
Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration.
Article in Bioactive materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- MSC-EVs in Cartilage Regeneration and Immunomodulation: Mechanisms and Therapeutic Prospects for Osteoarthritis, Rheumatoid Arthritis and Intervertebral Disc Degeneration.International journal of molecular sciences · 2026Review
- Surviving the Nucleus Pulposus Desert: Next-Generation Strategies for Intervertebral Disc Cell Therapy.JOR spine · 2026Article
- Dual-Gene Edited Extracellular Vesicles Remodel the Redox Homeostasis to Inhibit Ferroptosis in Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Challenge-Oriented Review of Delivery Systems for Cell and Gene Therapies in Intervertebral Disc Degeneration.Bioengineering (Basel, Switzerland) · 2026Review
- Mesenchymal stem cells and derived extracellular vesicles in major respiratory diseases: from multifaceted molecular mechanisms to clinical perspectives.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intervertebral disc degeneration (IDD) is a predominant contributor to spinal disorders. Previous studies have indicated that ferroptosis-induced senescence of nucleus pulposus cells (NPC) plays a critical role in IDD pathogenesis. This underscores therapeutic strategies aimed at inhibiting ferroptosis and delaying NPC senescence. Mesenchymal stem cell-derived exosomes (MSC-EVs), serving as a form of regenerative nanotherapy, inherit parental biological properties. In this study, we pretreated MSCs by simulating a senescent microenvironment to obtain "domesticated vesicles" (D-EVs) with enhanced targeting and anti-senescence properties. Multi-omics analysis revealed that D-EVs are enriched with GPX4 protein and achieve specific binding to senescent NPCs via the CXCL10-CXCR3 chemokine axis. Functionally, D-EVs delivered GPX4 protein to recipient NPCs, thereby inhibiting ferroptosis and alleviating cellular senescence. To enable sustained and on-demand release within the degenerative microenvironment, we anchored D-EVs to thermosensitive hydrogel via ROS-responsive peptides. This ROS-responsive hydrogel further potentiated D-EVs' efficacy in alleviating NPC ferroptosis and reversing senescence-associated metabolic dysfunction. Both in vitro and in vivo experiments revealed that this senescence-targeting system significantly suppresses ferroptosis and senescence pathways, and prevents conversion of the senescence phenotype in NPCs. This study presents a novel approach to inhibit ferroptosis, thereby delaying NPC senescence and mitigating IDD progression.
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