Effects and mechanisms of MSCs and MSC-derived exosomes in regulating ferroptosis

Ferroptosis is a kind of programmed cell death characterized by the iron-dependent lipid peroxides accumulation, playing a pivotal role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, and osteoporosis. Mesenchymal stem cells (MSCs) and MSCs-derived exosomes (MSC-exos) are actively implicated in key biological processes, such as inflammatory and immune responses, tissue regeneration and repair, and aging. Emerging studies highlight the potential of MSCs and MSC-exos as effective regulators of ferroptosis, offering novel strategies for targeted therapeutic intervention in ferroptosis-related pathologies. This review comprehensively explores the precise regulatory mechanisms by which MSCs and MSC-exos modulate ferroptosis. We also evaluate the impact of ferroptosis on MSC biological functions and MSC-exos release. Furthermore, the therapeutic potentials and advantages of engineered MSCs and MSC-exos in the treatment of various diseases have also been explored, emphasizing their mechanistic roles in ferroptosis modulation across different organs and systems. This review provides insights and future directions for the development of novel MSC- or MSC-exos-based therapeutic strategies targeting ferroptosis.