Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency
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...
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doaj-a599dfb54d1f4a198162c1f33313a6912021-02-26T07:45:57ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982021-02-0114217918510.18240/ijo.2021.02.0120210201Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiencyGuo-Hu Di0Xia Qi1Jing Xu2Chao-Qun Yu3Qi-Long Cao4Zhi-Jun Xing5Zhi-Chao Li6Zhi-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.comShandong Eye Institute, Qingdao 266071, Shandong Province, ChinaSchool of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, ChinaSchool of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, ChinaQingdao Haier Biotech Co. Ltd., Qingdao 266071, Shandong Province, ChinaQingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), Qingdao 266033, Shandong Province, ChinaDepartment of Gynecology and Obstetrics, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, ChinaAIM: 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.http://ies.ijo.cn/en_publish/2021/2/20210201.pdfmsc-cmtlimbal stem cell deficiencytsg-6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guo-Hu Di Xia Qi Jing Xu Chao-Qun Yu Qi-Long Cao Zhi-Jun Xing Zhi-Chao Li |
spellingShingle |
Guo-Hu Di Xia Qi Jing Xu Chao-Qun Yu Qi-Long Cao Zhi-Jun Xing Zhi-Chao Li Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency International Journal of Ophthalmology msc-cmt limbal stem cell deficiency tsg-6 |
author_facet |
Guo-Hu Di Xia Qi Jing Xu Chao-Qun Yu Qi-Long Cao Zhi-Jun Xing Zhi-Chao Li |
author_sort |
Guo-Hu Di |
title |
Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency |
title_short |
Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency |
title_full |
Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency |
title_fullStr |
Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency |
title_full_unstemmed |
Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency |
title_sort |
therapeutic effect of secretome from tnf-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency |
publisher |
Press of International Journal of Ophthalmology (IJO PRESS) |
series |
International Journal of Ophthalmology |
issn |
2222-3959 2227-4898 |
publishDate |
2021-02-01 |
description |
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. |
topic |
msc-cmt limbal stem cell deficiency tsg-6 |
url |
http://ies.ijo.cn/en_publish/2021/2/20210201.pdf |
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