The Anti‐Inflammatory and Anti‐Angiogenic Role of Mesenchymal Stem Cells in Corneal Wound Healing Following Chemical Injury

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), MSC applied topically to the damaged corneas for 2 hours immediately after the injury or MSC‐CM applied either once or 3 times per day for 3 consecutive days. Corneal surface was evaluated every week. After 3 weeks, the corneas were stained with the hematoxylin‐eosin, and the expression of interleukin (IL)‐2, interferon (IFN)‐γ, IL‐6, IL‐10, transforming growth factor (TGF)‐β1, 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‐γ, although increased IL‐10 and TGF‐β1 as well as IL‐6, (3) reduced the infiltration of CD4+ cells, and (4) upregulated the expression of TSP‐1, although downregulated that of MMP‐2. Interestingly, whereas three‐time application of MSC‐CM was partially effective, transplantation of MSC achieved a better outcome in suppressing corneal inflammation. 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‐β1, IL‐6 and TSP‐1. Disclosure of potential conflicts of interest is found at the end of this article.