Mesenchymal stem cell-derived extracellular vesicles for disease therapy by regulating ferroptosis: focus on diabetes mellitus and diabetic complications

Ferroptosis is a novel form of programmed cell death, which has been demonstrated to play a pivotal role in various pathological processes due to its association with iron overload, lipid peroxidation, and dysregulation of the antioxidant system. In recent years, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered significant attention as a promising cell-free therapeutic strategy for modulating ferroptosis. This article elucidates the biological characteristics of MSC-EVs and the molecular mechanisms underlying ferroptosis, with a focus on how MSC-EVs regulate ferroptosis through three key pathways: iron metabolism, lipid metabolism, and the antioxidant defense system. Additionally, the therapeutic potential of both natural and engineered MSC-EVs in treating ferroptosis-related diseases is discussed, particularly highlighting their efficacy in diabetes mellitus and diabetic complications. Finally, this article evaluates the challenges and opportunities in translating MSC-EVs-based ferroptosis modulation therapies into clinical applications, providing valuable insights for future research and therapeutic development.