Mesenchymal Stem Cell-Derived Exosomes in Anti-NET Therapy: Mechanisms, Challenges, and Future Perspectives

Neutrophils, a key component of the innate immune system, play a crucial role in immune responses. In 2004, Brinkmann et al identified neutrophil extracellular traps (NETs) as a novel antibacterial mechanism. However, NETs have since been implicated in the pathogenesis of various diseases, including autoimmune disorders, sepsis, and cancer. Consequently, targeting NETs has emerged as a promising therapeutic approach. Mesenchymal stem cells (MSCs) have demonstrated efficacy in modulating NET formation, but MSC-derived exosomes offer distinct advantages over whole MSCs due to their lower immunogenicity, higher biological stability, and ability to deliver bioactive molecules like miRNAs and CD59. These exosomes can block critical signaling pathways involved in NET formation and protect neutrophil mitochondria, inhibiting NET release. Despite challenges such as low yield and targeting efficiency, ongoing research has made significant strides in addressing these issues. This article reviews the current progress in MSC-derived exosome-based anti-NET therapies and discusses potential strategies to enhance their therapeutic application.