Bone mesenchymal stem cells based on matric hydrogels attenuate intervertebral disc degeneration by suppressing oxidative stress-induced ferroptosis

Abstract

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.

Keywords

• Intervertebral disc degeneration
• Bone mesenchymal stem cell
• Matric hydrogels
• Ferroptosis
• STAT3