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Alireza Mashaghi-Tabari, Reza Dana, Sunil Chauhan; Mesenchymal stem cells suppress innate immune response to corneal injury. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4356.
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© ARVO (1962-2015); The Authors (2016-present)
Mesenchymal stem cells (MSC) are the main stromal cell population in the bone marrow and possess significant regenerative and immunomodulatory capacities. MSCs have been shown to modulate the host adaptive immune response, but their effect on the innate response is largely unknown. Here, we aimed to investigate the immunomodulatory effect of MSCs on innate immune system, specifically on neutrophils, using a mouse model of corneal injury.
Corneal injury was introduced to male C57BL/6 mice by removing the epithelium and the basement membrane from the central cornea using an Algerbrush II. Mesenchymal stem cells (CD45-CD34-SCA1+CD29+) were isolated from syngeneic bone marrow and were administered intravenously 3 hours after the injury. The draining lymph nodes and corneas of naïve mice, MSC-treated and non-treated (control) injured mice were analyzed for CD11b+ cells, neutrophils (CD11b+ Ly6Clo Ly6Ghi) and macrophages (CD11b+ Ly6Chi Ly6G-) 36 hours post-injury using flow cytometry.
Injury to the cornea increased the frequencies of corneal CD11b+ cells by 10-fold. In MSC-treated mice, the frequencies of corneal CD11b+ cells were nearly half of that observed in non-treated mice. Phenotypic analysis showed that the majority (~90%) of CD11b+ cells in healthy corneas are Ly6G- LY6C-, while injured corneas showed 10-fold increase in the frequencies of neutrophils (CD11b+ Ly6Clo Ly6Ghi) and macrophages (CD11b+ Ly6Chi Ly6G-). We found that MSC administration reduced the frequencies of neutrophils and macrophages by 50%. Finally, MSCs administration was found to reduce CD11b+ cells in the draining lymph nodes by 40%.
Our data clearly demonstrate that MSCs have the capacity to regulate innate immune response via inhibiting the migration of neutrophils and macrophages to injured corneas.
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