Abstract
Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
