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Updated: Jun 25, 2026

Isolation and Identification of Limbal Niche Cells
Published on: October 27, 2023
Cytokine secretion by human mesenchymal stem cells cocultured with damaged corneal epithelial cells
Joo Youn Oh1, Mee Kum Kim, Mi Sun Shin
1Department of Ophthalmology, Seoul National University College of Medicine, 28 Yeongeon-dong, Chongno-gu, Seoul 110-744, Republic of Korea.
Abstract:
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.
Insights
Mesenchymal stem cells (MSCs) modulate corneal inflammation and blood vessel growth. Cocultures revealed MSCs increase interleukin-6 and vascular endothelial growth factor, crucial for these processes.
Area of Science:
- Ophthalmology
- Stem Cell Biology
- Immunology
Background:
- Mesenchymal stem cells (MSCs) show therapeutic potential in corneal diseases.
- Previous studies indicated MSCs reduce corneal inflammation and neovascularization via paracrine signaling.
Purpose of the Study:
- To identify specific molecules responsible for MSC-mediated effects on corneal inflammation and neovascularization.
- To analyze cytokine secretion profiles of MSCs in various co-culture conditions.
Main Methods:
- Co-culturing human MSCs with human peripheral blood mononuclear cells (hPBMCs) and/or chemically-damaged human corneal epithelial cells (hCECs).
- Analyzing cytokine secretion profiles, including interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinases (MMP-2, MMP-9), thrombospondin-1, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and IL-10.
Main Results:
- MSC co-cultures with hCECs significantly increased IL-6 and VEGF secretion from MSCs.
- Addition of hPBMCs further enhanced IL-6 and VEGF levels.
- MSCs constitutively expressed TGF-beta1, MMP-2, and thrombospondin-1.
- MSCs suppressed MMP-9 secretion by hCECs.
Conclusions:
- The study identifies IL-6 and VEGF as key candidate molecules mediating MSCs' anti-inflammatory and anti-angiogenic effects in the cornea.
- These findings provide insights into the molecular mechanisms of MSC-based therapies for corneal injuries.
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