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Rui Zhang, Yan Sun, Eric Pearlman, Suber S Huang; Bacterial induced corneal inflammation is inhibited by Mesenchymal Stem Cells (MSCs). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):942.
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Numerous studies have demonstrated inflammation to play a key role in the development of pathologic ocular scarring. Mesenchymal stem cells (MSCs) have been shown in recent research to help with the healing response in various diseases. This study evaluates whether the targeted delivery of MSCs decreases the amount of pathologic and inflammatory response to ocular injury using a bacterial infection model.
C57BL/6 mice corneas were abraded, and infection was induced by Pseudomonas aeruginosa. The mice were divided into 3 groups. One group received topical antibiotic (moxifloxacin) 2 hrs post procedure, then every 12 hrs for 24 hrs; one group received Human-derived Mesenchymal Stem Cells (MSCs) and the third group received topical moxifloxacin and MSCs. The human derived MSCs were injected into the subconjunctival space immediately after bacterial innoculation. Progression of corneal changes was followed with clinical photos. The mice were sacrificed on day 7, and the degree of corneal infiltration and inflammation was studied via confoscan and histological sections, and neutrophil recruitment to the corneal stroma was detected by immunohistochemistry.
The corneas of mice treated with MSCs and antibiotic displayed less stromal edema, infiltration and clinical disease on day 2 and 5 after treatment. Confoscan data at day 7 showed that mice treated with MSC and antibiotic had significantly less stromal haze and thickness with a P<0.05 when compared to mice treated with antibiotics. Clinical photos taken on day 7 also displayed less disease, scarring, and inflammation in mice treated with MSCs and antibiotic versus antibiotic alone. Immunohistochemistry performed on corneal sections also showed less neutrophil recruitment and disruption of overall structure in mice treated with both MSCs and antibiotic.
These results suggest that the local delivery of MSCs may be an effective and safe way to supplement and immunomodulate the ocular inflammatory process driven by the innate and adaptive immune responses. MSCs have little immunogenicity, do not require HLA typing, and has already been used intravenously in humans without serious consequences. These results hold promise for future clinical trials using MSCs in ocular keratitis and other inflammatory diseases, such as being primary or an adjunctive treatment for neovascular age related macular degeneration.
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