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Subconjunctival injection of tumor necrosis factor-α pre-stimulated bone marrow-derived mesenchymal stem cells enhances anti-inflammation and anti-fibrosis in ocular alkali burns

  • Basic Science
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Abstract

Purpose

To investigate the therapeutic effect of subconjunctival injection of tumor necrosis factor-α (TNF-α) pre-stimulated bone marrow-derived mesenchymal stem cells (BMMSCs) on ocular alkali burns in a rat model.

Methods

After applying a 6 mm filter paper soaking in 1 N NaOH on the cornea of rats, the suspension of TNF‐α pre-stimulated BMMSCs, BMMSCs and PBS were given subconjunctivally and respectively. Corneal epithelial defect, corneal opacity, inflammation as well as PTGS2 and TSG-6 expression on day 7 and fibrosis on day 14 were compared.

Results

TNF‐α pre-stimulated BMMSCs group had a more predominate effect on promoting corneal epithelial repairing, decreasing corneal opacity, reducing inflammatory cells and CD68 + macrophages on day 7 and suppressing fibrosis on day 14 compared to BMMSCs group. Besides, it had significant increased expressions of PTGS2 and TSG-6 in vitro. Pre-treated with Indomethacin revealed a reverse effect on above-mentioned changes.

Conclusion

Subconjunctival injection of TNF‐α pre-stimulated BMMSCs enhanced anti-inflammatory and anti-fibrotic effect in ocular alkali burns, which was possibly though up regulation of PTGS2 and TSG-6 expression.

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Data availability

The datasets generated and analyzed during the present study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the grants from Technological Project Foundation of Guangdong Province (2014B020226003) and from the National Natural Science Foundation of China (81770892).

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Author notes

  1. Nuan Zhang and Xiaohui Luo contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China

    Nuan Zhang, Xiaohui Luo, Shiyao Zhang, Ren Liu, Lingyi Liang, Wenru Su & Dan Liang

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  1. Nuan Zhang
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  2. Xiaohui Luo
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  3. Shiyao Zhang
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  4. Ren Liu
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  7. Dan Liang
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Contributions

Dan Liang, Wenru Su, Xiaohui Luo and Lingyi Liang designed the study; Nuan Zhang, Xiaohui Luo, Shiyao Zhang and Ren Liu conducted the study, collected, analyzed and interpreted data; Nuan Zhang preparation and writing the manuscript; Lingyi Liang, Wenru Su and Dan Liang review and approval of the manuscript.

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Correspondence to Lingyi Liang, Wenru Su or Dan Liang.

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This animal study was approved by the Institutional Animal Care and Use Committee (Ethics Number: 2016–013) of Zhongshan Ophthalmic Center, Sun Yat-sen University.

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Zhang, N., Luo, X., Zhang, S. et al. Subconjunctival injection of tumor necrosis factor-α pre-stimulated bone marrow-derived mesenchymal stem cells enhances anti-inflammation and anti-fibrosis in ocular alkali burns. Graefes Arch Clin Exp Ophthalmol 259, 929–940 (2021). https://doi.org/10.1007/s00417-020-05017-8

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  • DOI: https://doi.org/10.1007/s00417-020-05017-8

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