The Immunomodulatory Role of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Asthma.

Asthma is a chronic respiratory disease characterized by airway inflammation, hyperresponsiveness, and remodeling. Its pathogenesis is mainly related to immune imbalance, including Th1/Th2 and Th17/Treg imbalance, ILC2 activation and macrophage polarization, all of these contribute to airway inflammation and epithelial damage. Existing glucocorticosteroids and biologics have limited efficacy in non-Th2 or steroid-resistant patients, therefore new immunomodulatory strategies are urgently needed. Mesenchymal stem cell-derived exosomes (MSC-Exos), especially human umbilical cord MSC-Exos (HUCMSC-Exos), can regulate immune cell function, inhibit inflammasome activation, promote epithelial repair and attenuate airway remodeling and oxidative stress through a variety of active molecules such as proteins, miRNAs, lncRNAs and lipids. In animal and in vitro studies, MSC-Exos have shown good anti-inflammatory, immunomodulatory and tissue-protective effects, as well as low immunogenicity and good biocompatibility, providing a basis for clinical application. MSC-Exos are expected to become an innovative therapeutic strategy for asthma, especially for severe and steroid-resistant patients. However, the vast majority of current evidence remains limited to animal experiments and in vitro studies, and large-scale randomized controlled clinical trials are still lacking to verify its safety, efficacy, and standardized administration regimens in humans. Future researches should focus on defining the active ingredients, optimizing preparation and delivery methods, and conducting clinical validation to achieve multi-targeted and individualized immune interventions.