Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis
Abstract Intervertebral disc degeneration (IVDD) and its attendant lower back pain are a major medical challenge. Ferroptosis has become a new target for the treatment of IVDD. Mesenchymal stem cells (MSCs) are a promising regenerative therapy for IVDD. Hydrogel is usually used as a delivery carrier...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-00278-x |
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| Summary: | Abstract Intervertebral disc degeneration (IVDD) and its attendant lower back pain are a major medical challenge. Ferroptosis has become a new target for the treatment of IVDD. Mesenchymal stem cells (MSCs) are a promising regenerative therapy for IVDD. Hydrogel is usually used as a delivery carrier for MSCs. This study investigated the effect of bone mesenchymal stem cells (BMSCs) in IVDD by magnetic resonance imaging (MRI) and hematoxylin and eosin (HE) staining analysis using a rat-punctured IVDD model. A vitro model of tert-butyl hydroperoxide (TBHP)-induced oxidative stress injury in annulus fibrosus cells (AFCs) was used to explore the underlying molecular mechanisms. Cell viability was detected by cell counting kit-8 assay. Ferroptosis was assessed by measuring the levels of LDH, Fe2+, glutathione, lipid reactive oxygen species, and malondialdehyde. The underlying mechanism was investigated by western blot and phosphor-kinase array. Results suggested that BMSCs inhibited TBHP-induced ferroptosis and the phosphorylated levels of STAT3 in AFCs. The activation of STAT3 (colivelin, a specific agonist for STAT3) reversed the effects on the ferroptosis of BMSCs. Additionally, BMSCs alleviated IVDD progression based on matrix hydrogels, while colivelin abolished the protective effects of BMSCs-encapsulated hydrogels on IVDD. In short, BMSCs inhibited oxidative stress-induced AFCs ferroptosis, thereby alleviating IVDD, which is associated with inhibited STAT3 activation. This study demonstrated the possible underlying mechanism by which BMSCs mitigate IVDD and may provide a new therapeutic idea for IVDD. |
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| ISSN: | 2045-2322 |