Experts Develop Strategy Involving Suppressing Cell Senescence For Treating Disc Degeneration
Disc degeneration is a common pathology for various degenerative spinal disorders, characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation. However, effective treatments for disc degeneration are currently unavailable. Recently, Prof. WANG Yue from the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU) published an article in ACS Nano, entitled “A Redox Homeostasis Modulatory Hydrogel with GLRX3+ Extracellular Vesicles Attenuates Disc Degeneration by Suppressing Nucleus Pulposus Cell Senescence”. The study presents a novel approach to suppressing cell senescence and attenuating disc degeneration by regulating the redox balance of NP cells.
Growing evidence suggests that oxidative stress, a state in which intracellular reactive oxygen species (ROS) levels exceed physiological thresholds, may be the “chief culprit” leading to disc degeneration. The study demonstrates that the deficiency of the redox-regulating molecule GLRX3 leads to increased intracellular ROS and a subsequent senescent NP phenotype.
Using a hypoxic preconditioning method, the team developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense. Replenishing EVs-GLRX3 can balance redox homeostasis and attenuate mitochondrial damage and, thus, alleviate NP cell senescence.
Furthermore, this study found EVs-GLRX3 were promising nanotherapeutics for replenishing GLRX3 in NP cells and were delivered using a GDC hydrogel with ROS scavenging and responsive properties to the disc for treating disc regeneration.
The developed GDC@EVs-GLRX3 is an injectable redox homeostasis modulatory hydrogel system, which exhibits high efficiency in decreasing local senescence state, and restoring the matrix deposition of NP cells via ROS microenvironment mitigation.
Overall, this work provides a proof-of-concept that an injectable redox homeostasis modulatory hydrogel system may have prophylactic and therapeutic potential for treating disc degeneration by attenuating NP cellular senescence.