The Effects of Mesenchymal Stem Cell-Derived Exosomes on the Attenuation of Dry Eye Disease in Sjögren Syndrome Animal Model.

BACKGROUND: Sjögren's syndrome (SS) is a chronic autoimmune disease delineated by excessive lymphocyte infiltration to the lacrimal or salivary glands, leading to dry eye and dry mouth. Exosomes secreted from mesenchymal stem cells (MSC) are known to have anti-inflammatory and tissue regeneration abilities. This study endeavored to demonstrate the effect of MSC-derived exosomes on the clinical parameter of dry eyes and associated pathology in SS mouse model. METHODS: Exosomes obtained from bone marrow-derived human MSC (Catholic MASTER Cells) were injected into the subconjunctival sac of 17 weeks-old NOD/LtJ female mice once and sacrificed after 7 days, or administered topically as an eyedrop every day for 14 days, then sacrificed. Clinical dry eye parameters, including tear volume and corneal staining scores, density of goblet cells in the conjunctiva, pro-inflammatory cytokine expressions of cornea and conjunctiva, and the lacrimal glands were evaluated. Infiltration of inflammatory foci, and expression of B and T cells in the lacrimal glands were examined. RESULTS: Tear volume, corneal stain scores and density of goblet cells in conjunctiva were improved in the exosome-treated groups compared to the control group. Pro-inflammatory cytokine expressions were also reduced in the cornea and conjunctiva of the exosome-treated group. In the lacrimal glands of the exosome-treated mice, inflammatory foci infiltration and B cell marker expressions were significantly decreased. CONCLUSIONS: Thus, this study demonstrated the amelioration of dry eyes with the administration of exosomes in SS animal model, suggesting promising therapeutic potential of MSC-derived exosomes in SS dry eyes.