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Afsaneh Amouzegar, Sharad Mittal, Sunil Chauhan; Mesenchymal stem cells modulate the differentiation of myeloid progenitor cells in corneal inflammation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1434.
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© ARVO (1962-2015); The Authors (2016-present)
Mesenchymal stem cells (MSCs) display unique anti-inflammatory and immunomodulatory properties and have potential therapeutic applications in various inflammatory diseases. The purpose of this study was to investigate the effect of MSCs on maturation and differentiation of myeloid progenitor cells in corneal inflammation.
Mesenchymal stem cells were generated from bone marrow of wild-type C57BL/6 mice, and characterized by flow cytometry for the expression of CD29+SCA1+CD45−CD34−. Corneal injury was induced by mechanical removal of the corneal epithelium and anterior stroma. For in vitro assays, murine myeloid progenitor cells (CD34+CD14+CD11b–Ly6G–Ly6C–) were sorted from the spleen using flow cytometry. In order to investigate the effect of MSCs on corneal inflammation, MSCs were intravenously injected to mice with corneal injury. Frequencies of myeloid progenitor cells and CD11b+ cells in the injured cornea were determined after 48 hours. To further investigate immunomodulatory function of MSCs, myeloid progenitors were co-cultured with MSCs in the presence of IFNγ for 72 hours. Myeloid progenitor cell acquisition of CD11b (αM integrin) and their further differentiation into monocytic (Ly6Chi Ly6G–) vs. granulocytic (Ly6Clo Ly6G+) lineage of suppressor cells was assessed using flow cytometry.
Systemic administration of MSCs in mice with corneal injury resulted in a 2-fold increase in the frequencies of corneal myeloid progenitor cells, and a significant 50% decrease in the frequencies of corneal CD11b+ cells compared to injured mice without MSC treatment. Myeloid progenitor cells co-cultured with MSCs demonstrated a significant 68% reduction in CD11b (αM integrin) acquisition compared to progenitors cultured without MSCs (4.3±1.6% vs 13.4±4.6%; p<0.001). Interestingly, the majority of these CD11b expressing cells demonstrated a phenotype of monocytic Ly6Chi Ly6G– suppressor cells (64.1±5.8%) compared to CD11b+ cells differentiated from progenitors co-cultured without MSCs (23.7±4.7%; p<0.001).
Our data suggest that MSCs modulate corneal inflammation by reducing CD11b+ cell frequencies in the injured cornea, and by promoting differentiation of myeloid progenitor cells toward anti-inflammatory monocytic suppressor cells.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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