Mesenchymal stem cell-derived exosomes as a potential therapeutic strategy for ferroptosis.

Abstract

Ferroptosis, a regulated type of cell death directed by iron-dependent lipid peroxidation, is associated with a variety of pathological diseases. Recent findings have highlighted the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-Exos) in modulating ferroptosis. These nano-sized extracellular vesicles carry bioactive substances, including proteins, lipids, and microRNAs, which regulate vital pathways related to ferroptosis, such as reactive oxygen species production, glutathione metabolism, and lipid peroxidation. Preclinical studies suggest that MSC-Exos can alleviate ferroptosis-induced damage by enhancing antioxidant defenses, mitigating oxidative stress, upregulating anti-ferroptotic regulators, and suppressing lipid peroxidation. Notably, in cancer, MSC-Exos may protect non-malignant tissues from chemotherapy-induced ferroptosis. By exploiting their regenerative and immunomodulatory properties, MSC-Exos offer a promising therapeutic platform for targeting ferroptosis in diverse pathological conditions. This review summarizes the biological and functional characteristics of MSC-Exos, elucidates their roles in ferroptosis regulation across multiple disease models, and discusses current challenges and future directions for clinical translation.