Therapeutic strategies for intervertebral disc degeneration: Extracellular vesicles and microRNAs derived from mesenchymal stem cells.

Intervertebral disc degeneration (IDD) results from an imbalance within the intervertebral disc, leading to alterations in extracellular matrix composition, loss of nucleus pulposus cells, increased oxidative stress, and inflammatory cascade. While IDD naturally progresses with age, some factors such as mechanical trauma, lifestyle choices, and genetic abnormalities can elevate the risk of symptomatic disease progression. Current treatments, including pharmacological and surgical interventions, fail to halt disease progression or restore IDD function. Although biological therapies have been evaluated, their effectiveness in reversing long-term disc degeneration remains inconsistent. Mesenchymal stem cell-based therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations, ethical issues, To date, mesenchymal stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutic agents for regeneration and anti-inflammation. Their therapeutic effects are attributed to several mechanisms, such as the induction of regenerative phenotype, apoptosis mitigation, and immunomodulation. In addition, the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration. Due to the problems in clinical use, however, the efficiency of the EVs should be overcome further by optimizing cell culture conditions, engineering them to deliver drugs and targeting molecules,