Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency
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Zhi-Chao Li. Department of Gynecology and Obstetrics, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China. lizhichao_0607@126.com; Zhi-Jun Xing. Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), Qingdao 266033, Shandong Province, China. xing197968@163.com

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Supported by the National Natural Science Foundation of China (No.81670829); Shandong Provincial Natural Science Fund (No.ZR2018PH020).

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    Abstract:

    AIM: To explore the secretome efficacy in tumor necrosis factor (TNF)-α stimulated mouse mesenchymal stem cells (MSCs) in a murine model of corneal limbal alkali injury. METHODS: Corneal limbal stem cell deficiency (LSCD) was created in the eyes of male C57 mice. Concentrated conditioned medium from TNF-α stimulated MSCs (MSC-CMT) was applied topically for 4wk, with basal medium and conditioned medium from MSCs as controls. Corneal opacification, corneal inflammatory response, and corneal neovascularization (NV) were evaluated. Corneal epithelial cell apoptosis, corneal conjunctivation, and inflammatory cell infiltration were assessed with TUNEL staining, CK3 and Muc-5AC immunostaining, and CD11b immunofluorescence staining, respectively. The effect of TSG-6 was further evaluated by knockdown with short hairpin RNA (shRNA). RESULTS: Compared to the controls, topical administration of MSC-CMT significantly ameliorated the clinical symptoms of alkali-induced LSCD, with restrained corneal NV, reduced corneal epithelial cell apoptosis, and inhibition of corneal conjunctivation. In addition, MSC-CMT treatment significantly reduced CD11b+ inflammatory cell infiltration, and inhibited the expression of pro-inflammatory cytokines (IL-1β, TNF-α and IL-6). Furthermore, the promotion of corneal epithelial reconstruction by MSC-CMT was largely abolished by TSG-6 knockdown. CONCLUSION: Our study provides evidence that MSC-CMT enhances the alleviation of corneal alkali injuries, partially through TSG-6-mediated anti-inflammatory protective mechanisms. MSC-CMT may serve as a potential strategy for treating corneal disorders.

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Guo-Hu Di, Xia Qi, Jing Xu, et al. Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency. Int J Ophthalmol, 2021,14(2):179-185

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Publication History
  • Received:July 02,2020
  • Revised:September 03,2020
  • Adopted:
  • Online: December 24,2020
  • Published: