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The Immunomodulatory Potential of Mesenchymal Stem Cells in a Retinal Inflammatory Environment

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Abstract

Retinal degenerative disorders are characterized by a local upregulation of inflammatory factors, infiltration with cells of the immune system, a vascular dysfunction and by the damage of retinal cells. There is still a lack of treatment protocols for these diseases. Mesenchymal stem cell (MSC)-based therapy using immunoregulatory, regenerative and differentiating properties of MSCs offers a promising treatment option. In this study, we analyzed the immunomodulatory properties of mouse bone marrow-derived MSCs after their intravitreal delivery to the inflammatory environment in the eye, caused by the application of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ. The intravitreal administration of these cytokines induces an increased expression of pro-inflammatory molecules such as IL-1α, IL-6, inducible nitric oxide synthase, TNF-α and vascular endothelial growth factor in the retina. However, a significant decrease in the expression of genes for all these pro-inflammatory molecules was observed after the intravitreal injection of MSCs. We further showed that an increased infiltration of the retina with immune cells, mainly with macrophages, which was observed after pro-inflammatory cytokine application, was significantly reduced after the intravitreal application of MSCs. The similar immunosuppressive effects of MSCs were also demonstrated in vitro in cultures of cytokine-stimulated retinal explants and MSCs. Overall, the results show that intravitreal application of MSCs inhibits the early retinal inflammation caused by pro-inflammatory cytokines, and propose MSCs as a promising candidate for stem cell-based therapy of retinal degenerative diseases.

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Acknowledgements

This work was supported by grants from the Grant Agency of the Czech Republic no. 17-04800S, 18-04393S and 19-02290S, the projects from the Ministry of Education, Youth and Sports of the Czech Republic no. SVV 244-260435, NPU-I: LO1508 and NPU-I: LO1309 and project from the Grant Agency of the Charles University no. 1516218 and 1184119.

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Authors and Affiliations

  1. Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20, Prague 4, Czech Republic

    Barbora Hermankova, Jan Kossl, Pavla Bohacova, Eliska Javorkova, Michaela Hajkova, Magdalena Krulova, Alena Zajicova & Vladimir Holan

  2. Department of Cell Biology, Faculty of Science, Charles University, 128 43, Prague 2, Czech Republic

    Jan Kossl, Pavla Bohacova, Eliska Javorkova, Michaela Hajkova, Magdalena Krulova & Vladimir Holan

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  1. Barbora Hermankova
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Correspondence to Vladimir Holan.

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All applicable national and institutional guidelines for the care and use of animal were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution and was approved by the local Animal Ethics Committee of the Institute of Experimental Medicine.

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Hermankova, B., Kossl, J., Bohacova, P. et al. The Immunomodulatory Potential of Mesenchymal Stem Cells in a Retinal Inflammatory Environment. Stem Cell Rev and Rep 15, 880–891 (2019). https://doi.org/10.1007/s12015-019-09908-0

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