The Anti-inflammatory and Anti-angiogenic Role of Mesenchymal Stem Cells in Corneal Wound Healing Following Chemical Injury

¹ Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital Clinical Research Institute, Seoul, Korea
² Seoul National University Hospital Clinical Research Institute, Seoul, Korea

^* To whom correspondence should be addressed. E-mail: kmk9{at}snu.ac.kr.

	Abstract

To investigate the anti-inflammatory and anti-angiogenic effects of mesenchymal stem cells (MSC) in the chemically burned corneas, we mechanically removed the corneal epithelium of rats after 100% alcohol instillation. The rats were then randomized into four groups: fresh media, conditioned media derived from the MSC culture (MSC-CM) or MSC were applied topically to the damaged corneas for two hours immediately after the injury. MSC-CM was applied either once or three times per day for three consecutive days. Corneal surface was evaluated every week. After three weeks, the corneas were stained with the hematoxylin-eosin and the expression of interleukin (IL)-2, interferon (IFN)-, IL-6, IL-10, transforming growth factor (TGF)-1, thrombospondin-1 (TSP-1), matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) were analyzed. CD4⁺ cells were assessed in the corneas. We found that both MSC and three-time applied MSC-CM (1) reduced corneal inflammation and neovascularization, (2) decreased IL-2 and IFN-, while increased IL-10 and TGF- 1 as well as IL-6, (3) reduced the infiltration of CD4⁺ cells, and (4) upregulated the expression of TSP-1, while downregulated that of MMP-2. Interestingly, whereas three-time application of MSC-CM was partially effective to suppress corneal inflammation, transplantation of MSC achieved a better outcome. The results of this study suggest that the anti-inflammatory and anti-angiogenic action of MSC in the chemically burned corneas might be mediated in part through paracrine pathways involving soluble factors such as IL-10, TGF-1, IL-6 and TSP-1.

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