Cytokine secretion by human mesenchymal stem cells cocultured with damaged corneal epithelial cells.

We have previously shown that mesenchymal stem cells (MSCs) reduced corneal inflammation and neovascularization in chemically-burned rat corneas in part through paracrine action. In order to identify the molecule(s) involved, we cocultured human MSCs in the following conditions, and examined the alterations in the cytokine secretion profile; (1) human peripheral blood mononuclear cells (hPBMCs), (2) chemically-damaged human corneal epithelial cells (hCECs), (3) hPBMCs/hCECs, (4) hMSCs, (5) hMSCs/hPBMCs, (6) hMSCs/hCECs, (7) hMSCs/hPBMCs/hCECs. We found that the levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) by hMSCs markedly increased for hMSC/hCEC cocultures, and this elevation was further remarkable by the addition of hPBMCs. The hMSCs constitutively expressed transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP)-2, and thrombospondin-1. The secretion of MMP-9 by hCECs was significantly suppressed by hMSCs. Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and IL-10 were not detectable in any cultures. The data presented herein provide the candidate molecules mediating the MSC-mediated modulation of inflammation and angiogenesis in cornea.