| Literature DB >> 29301108 |
Hyun Beom Song1, Se Yeon Park2, Jung Hwa Ko2, Jong Woo Park2, Chang Ho Yoon2, Dong Hyun Kim3, Jeong Hun Kim4, Mee Kum Kim2, Ryang Hwa Lee5, Darwin J Prockop5, Joo Youn Oh6.
Abstract
The cornea is a transparent tissue devoid of blood and lymphatic vessels. However, various inflammatory conditions can cause hemangiogenesis and lymphangiogenesis in the cornea, compromising transparency and visual acuity. Mesenchymal stem/stromal cells (MSCs) have therapeutic potentials in a variety of diseases because of anti-inflammatory properties. Herein, we investigated the effects of MSCs on corneal angiogenesis using a model of suture-induced inflammatory corneal neovascularization. Data demonstrated that an intravenous administration of MSCs suppressed corneal inflammation and neovascularization, inhibiting both hemangiogenesis and lymphangiogenesis. MSCs reduced the levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, Tek, MRC1, and MRC2 in the cornea, which are expressed by pro-angiogenic macrophages. Moreover, the number of CD11b+ monocytes/macrophages in the cornea, spleen, peripheral blood, and draining lymph nodes was decreased by MSCs. Depletion of circulating CD11b+ monocytes by blocking antibodies replicated the effects of MSCs. Importantly, knockdown of tumor necrosis factor alpha (TNF-α)-stimulated gene/protein 6 (TSG-6) in MSCs abrogated the effects of MSCs in inhibiting corneal hemangiogenesis and lymphangiogenesis and monocyte/macrophage infiltration. Together, the results suggest that MSCs inhibit inflammatory neovascularization in the cornea by suppressing pro-angiogenic monocyte/macrophage recruitment in a TSG-6-dependent manner.Entities:
Keywords: cornea; lymphangiogenesis; mesenchymal stem/stromal cells
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Year: 2017 PMID: 29301108 PMCID: PMC5763076 DOI: 10.1016/j.ymthe.2017.09.026
Source DB: PubMed Journal: Mol Ther ISSN: 1525-0016 Impact factor: 11.454