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TRANSLATIONAL AND CLINICAL RESEARCH

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

^aDepartment of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea;
^bSeoul National University Hospital Clinical Research Institute, Seoul, Korea

Key Words. Angiogenesis • Cornea • Inflammation • Mesenchymal stem cell

Correspondence: Mee Kum Kim, M.D., Ph.D., Department of Ophthalmology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea. Telephone: +82-2-2072-2665; Fax: +82-2-741-3187; e-mail: kmk9{at}snu.ac.kr

Received September 3, 2007; accepted for publication January 4, 2008.
First published online in STEM CELLS EXPRESS   January 10, 2008.



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)-, 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-, 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.

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