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Mesenchymal stromal cells inhibit inflammatory lymphangiogenesis in the cornea by suppressing macrophage in a TSG-6-dependent manner

Cited 56 time in Web of Science Cited 58 time in Scopus
Authors

Song, Hyun Beom; Park, Se Yeon; Ko, Jung Hwa; Park, Jong Woo; Yoon, Chang Ho; Kim, Dong Hyun; Kim, Jeong Hun; Kim, Mee Kum; Lee, Ryang Hwa; Prockop, Darwin J.; Oh, Joo Youn

Issue Date
2018-01
Publisher
Nature Publishing Group
Citation
Molecular Therapy, Vol.26 No.1, pp.162-172
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 proper- ties. 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-alpha)-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.
ISSN
1525-0016
URI
https://hdl.handle.net/10371/202853
DOI
https://doi.org/10.1016/j.ymthe.2017.09.026
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  • College of Medicine
  • Department of Medicine
Research Area 각막 및 외안부 질환, 백내장

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