Nrf2 activation: a key mechanism in stem cell exosomes-mediated therapies

Exosomes are nano-sized membrane extracellular vesicles which can be released from various types of cells. Exosomes originating from inflammatory or injured cells can have detrimental effects on recipient cells, while exosomes derived from stem cells not only facilitate the repair and regeneration of damaged tissues but also inhibit inflammation and provide protective effects against various diseases, suggesting they may serve as an alternative strategy of stem cells transplantation. Exosomes have a fundamental role in communication between cells, through the transfer of proteins, bioactive lipids and nucleic acids (like miRNAs and mRNAs) between cells. This transfer significantly impacts both the physiological and pathological functions of recipient cells. Nuclear factor erythroid 2–related factor 2 (Nrf2), a transcription factor, is able to mitigate damage caused by oxidative stress and inflammation through various signaling pathways. The positive effects resulting from the activation of the Nrf2 signaling pathway in different disorders have been documented in various types of literature. Studies have confirmed that exosomes derived from stem cells could act as Nrf2 effective agonists. However, limited studies have explored the Nrf2 role in the therapeutic effects of stem cell-derived exosomes. This review provides a comprehensive overview of the existing knowledge concerning the role of Nrf2 signaling pathways in the impact exerted by stem cell exosomes in some common diseases. Graphical Abstract