Intravitreal Application of Mesenchymal Stem Cell By-Products Does Not Ameliorate Experimental Autoimmune Uveitis

The study aimed to evaluate the therapeutic effects of mesenchymal stem cells and their by-products, including conditioned medium, extract and exosomes, on intraocular inflammation in experimental autoimmune uveitis. Uveitis was induced in the C57BL/6J mouse strain by administration of interphotoreceptor retinoid-binding protein, complete Freund's adjuvant and pertussis toxin. Mesenchymal stem cell-derived products (conditioned medium, extract and exosomes) were prepared and administered intravitreally at varying time points post-induction, primarily on day 14. Retinal inflammatory changes were monitored using fundus imaging, flow cytometry and RT-PCR analysis to evaluate clinical manifestation of inflammation, immune cell infiltration and gene expression of inflammatory markers. In vivo, administration of mesenchymal stem cell by-products did not ameliorate experimental autoimmune uveitis. On the contrary, treated eyes exhibited exacerbated inflammation, including increased immune cell infiltration and up-regulated pro-inflammatory gene expression (e.g., Gfap, Iba1, Il1b and Il17). In vitro studies suggested a trend towards anti-inflammatory effects of the conditioned medium, but these findings were not replicated in vivo. Control experiments on healthy eyes indicated that intravitreal trauma alone significantly contributed to inflammatory responses, irrespective of the substance injected. Intravitreal application of mesenchymal stem cell by-products did not demonstrate therapeutic benefits in the experimental autoimmune uveitis model and instead promoted inflammation. The results highlight the impact of administration-induced trauma and suggest that alternative delivery methods, such as systemic administration, may be more effective for mesenchymal stem cell-based therapies.