Regulating pyroptosis by mesenchymal stem cells and extracellular vesicles: A promising strategy to alleviate intervertebral disc degeneration*

Intervertebral disc degeneration (IVDD) is a main cause of low back pain (LBP), which can lead to disability and thus generate a heavy burden on society. IVDD is characterized by a decrease in nucleus pulposus cells (NPCs) and endogenous mesenchymal stem cells (MSCs), degradation of the extracellular matrix, macrophage infiltration, and blood vessel and nerve ingrowth. To date, the therapeutic approaches regarding IVDD mainly include conservative treatment and surgical intervention. However, both can only relieve symptoms rather than stop or revert the progression of IVDD, since the pathogenesis of IVDD is not yet clear. Pyroptosis, which is characterized by Caspase family dependence and conducted by the Gasdermin family, is a newly discovered mode of programmed cell death. Pyroptosis has been observed in NPCs, annulus fibrosus cells (AFCs), chondrocytes, MSCs, macrophages, vascular endothelial cells and neurons and may contribute to IVDD. MSCs are a kind of pluripotent stem cell that can be found in almost all tissues. MSCs have a strong ability to secrete extracellular vesicles (EVs), which contain exosomes, microvesicles and apoptotic bodies. EVs derived from MSCs play an important role in pyroptosis regulation and could be beneficial for alleviating IVDD. This review focuses on clarifying the regulation of pyroptosis to improve IVDD by MSCs and EVs derived from MSCs.