Human umbilical cord-derived mesenchymal stem/stromal cells via suprachoroidal injection: A novel approach for experimental uveitis treatment

Abstract

Uveitis is a group of vision-threatening inflammatory diseases, and current treatment options are mainly limited to corticosteroids, which often have side effects and do not address the underlying immune dysregulation. Mesenchymal stem/stromal cells cultivated in vitro have gained attention for their immune-regulating, neurotrophic, and tissue-regenerative properties, making them a promising candidate for treating uveitis. This study investigates the safety and efficacy of human umbilical cord derived mesenchymal stem/stromal cells (HUMSCs) combined with a novel suprachoroidal microinjector for targeted delivery in a rabbit model of experimental uveitis (EU). No significant clinical or histological changes were observed following HUMSCs injection in normal Chinichilla rabbit eyes. In the EU model, treatment with HUMSCs and triamcinolone acetonide (TA) significantly alleviated uveitis symptoms compared to phosphate-buffered saline, with notable improvements in anterior chamber inflammation and vitreous opacity scores. Both treatments also reduced the levels of inflammatory cytokines (TNF-α, VEGF, MIP-1α, IL-17A, bFGF) in the aqueous humor. Histological and immunofluorescence analyses showed decreased inflammatory cell infiltration and microglial activation. Additionally, RNA sequencing revealed that HUMSCs injection downregulated key genes in the Th17 differentiation pathway, which plays a critical role in the pathogenesis of EU. These findings establish the safety and efficacy of suprachoroidal injection of HUMSCs, highlighting their potential as an effective, targeted therapeutic approach for uveitis, with results comparable to TA.