Mesenchymal stem cell and exosome-based therapies for degenerative disc disease: from mechanisms to clinical translation

Degenerative disc disease (DDD) is a leading cause of chronic low back pain and disability worldwide, placing a significant burden on public health systems and economies. The pathogenesis of DDD is characterized by oxidative stress, chronic inflammation, dysregulated cell death, and impaired extracellular matrix (ECM) homeostasis, all of which contribute to the structural degradation and functional impairment of intervertebral discs. Current clinical treatments primarily offer palliative relief, underscoring the urgent need for regenerative therapies that address the underlying pathological mechanisms. Mesenchymal stem cells (MSCs) and their exosomes (Exos) have emerged as promising candidates for DDD therapy, as they stimulate ECM synthesis, regulate inflammation, and enhance cell survival. Furthermore, advanced biomaterials have been developed to create bioactive environments that enhance cell retention and facilitate controlled therapeutic delivery. This review provides a comprehensive overview of the molecular mechanisms driving DDD, evaluates MSC/Exo and biomaterial-based therapies, and explores emerging technologies for personalized treatment strategies aimed at restoring disc function, extending beyond symptomatic management.