MSC-Encapsulated Porous Microparticle Eye Drops for Autoimmune Dry Eye Disease Treatment in NOD Mice

This study presents a mesenchymal stem cell (MSC)-encapsulated porous alginate microparticle platform designed as a noninvasive eye-drop therapy for autoimmune dry eye disease (DED). Using microfluidic electrospray, RGD-modified alginate microcarriers (RGD-Alg@MSCs) were fabricated to encapsulate MSCs within interconnected porous structures that balance mechanical integrity and ocular comfort. In vitro, RGD-Alg@MSCs enhanced corneal epithelial cell viability, reduced apoptosis, and suppressed proinflammatory cytokine expression under hyperosmotic stress. RNA sequencing revealed that encapsulated MSCs exhibited reduced activation of inflammatory signaling pathways (JAK–STAT, MAPK, NF-κB) and upregulated cytoskeletal and migration-related genes. In vivo, topical administration in NOD mice restored tear production, reduced lymphocytic infiltration, and suppressed TH17-mediated inflammation. The system achieved improved MSC retention and immunomodulation compared to conventional delivery methods, representing a clinically translatable approach for ocular autoimmune therapy.