MSC-encapsulated porous microparticle eye drops for autoimmune dry eye disease treatment in NOD mice

Dry eye disease (DED) is characterized by chronic inflammation and an unstable tear film. Stem cells have shown potential for DED treatment, but the main challenge lies in improving cell delivery effectiveness. Here, we developed eye drops for autoimmune DED treatment using porous arginine-glycine-aspartic acid (RGD)-modified alginate microcarriers with mesenchymal stem/stromal cells (MSCs) (RGD-Alg@MSCs). These microcarriers provided a favorable microenvironment for large-scale cell expansion while maintaining stemness with ideal mechanical properties for ocular application. In vitro, RGD-Alg@MSCs demonstrated significantly enhanced therapeutic effects compared to conventional MSCs, including improved cell viability, reduced apoptosis and reactive oxygen species, and enhanced release of immunomodulatory factors. Transcriptomic analysis revealed distinct molecular mechanisms underlying these enhanced therapeutic effects. In the mouse model, RGD-Alg@MSCs exhibited prolonged ocular retention and enhanced tear production, promoted corneal healing, and suppressed inflammation by inhibiting dendritic cell activation and T_H17 differentiation. Our microcarrier system substantially improves stem cell delivery efficiency for treating autoimmune DED.