Protective effects of human umbilical cord mesenchymal stem cells-derived small extracelluar vesicles on corneal epithelial cells under hyperosmotic stress: Inhibition of oxidative damage and inflammation.

Dry eye disease (DED) is often associated with corneal epithelial injury under hyperosmotic stress, which contributes to epithelial cell apoptosis and delay wound healing. Human Umbilical Cord Mesenchymal Stem Cell-derived Small Extracellular Vesicles (hUC-MSCs-sEVs) have emerged as promising therapeutic agents due to their anti-inflammatory, anti-apoptotic, and regenerative properties. In this study, we isolated and characterized hUC-MSCs-sEVs and assessed their therapeutic potential in hyperosmotic corneal epithelial injury. We demonstrated that hUC-MSCs-sEVs significantly promoted human corneal epithelial cell proliferation and repair under hyperosmotic conditions, reducing oxidative stress and preserving mitochondrial function. Additionally, hUC-MSCs-sEVs inhibited the expression of pro-inflammatory cytokines IL-6 and IL-1β, as well as downregulated the cGAS-STING signaling pathway, a critical mediator of inflammation. These findings suggest that hUC-MSCs-sEVs may offer a novel therapeutic strategy for treating hyperosmotic stress-induced corneal epithelial damage by mitigating oxidative stress, preserving mitochondrial integrity, and modulating inflammatory responses.