Exosomes as therapeutic delivery vehicles for intervertebral disc degeneration: Mechanisms and applications

Abstract Lumbar intervertebral disc degeneration (IDD) is one of the primary causes of chronic low back pain. Its pathogenesis involves a complex cascade of interconnected molecular events, including inflammation, extracellular matrix dysregulation, oxidative stress, autophagy imbalance, apoptosis, and cellular senescence. Regenerative biological therapies, such as gene therapy, growth factors, cell-based injections, and tissue-engineered constructs, have attracted widespread attention for directly addressing IDD. Among these, direct injection of exosomes into degenerative discs is a promising and rapidly advancing strategy. As cell-derived nanoscale vesicles, exosomes exhibit low immunogenicity, low toxicity, ability to cross biological barriers, and excellent carrier properties, making them highly attractive for IDD treatment. In this review, we comprehensively discuss the biological characteristics of exosomes, including their sources, secretion mechanisms, and core advantages. We further summarize the mechanisms of action and key signaling pathways of exosomes from various sources. Finally, we address current challenges and propose future research directions.