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Exosomes from bone marrow-derived mesenchymal stem cells facilitate corneal wound healing via regulating the p44/42 MAPK pathway

  • Basic Science
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Abstract

Purpose

This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway.

Methods

The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected.

Results

BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo, the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury.

Conclusion

BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo. BMSC-Exos may be promising resources for promoting corneal wound healing.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Natural Science Foundation of China (No. 81200666).

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Author notes

  1. Jin Zhou and Yuanyuan Ding contributed equally.

Authors and Affiliations

  1. Department of Ophthalmology, Guangzhou Women and Children’s Medical Center, No. 9, Jinsui Road, Tianhe District, Guangzhou City, 510623, China

    Jin Zhou, Dehui Zheng, Lifeng Yan, Mengxiang Guo, Yani Mao & Lihong Yang

  2. Department of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou City, 510515, China

    Yuanyuan Ding

  3. Department of Ophthalmology, Beijing Children’s Hospital East Branch, Beijing City, 100002, China

    Yongqiang Zhang

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  1. Jin Zhou
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Contributions

Jin Zhou: conceptualization; Yongqiang Zhang: methodology; Dehui Zheng and Lifeng Yan: formal analysis and investigation; Jin Zhou and Yuanyuan Ding: writing—original draft preparation; Mengxiang Guo and Yongqiang Zhang: writing—review and editing; Jin Zhou: funding acquisition; Yani Mao and Lihong Yang: resources; Yuanyuan Ding: supervision.

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Correspondence to Jin Zhou.

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This study complied with the National Institutes of Health's guidelines for the care and use of laboratory animals. This study was approved by the Animal Ethics Committee of Guangzhou Women and Children’s Medical Center.

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Zhou, J., Ding, Y., Zhang, Y. et al. Exosomes from bone marrow-derived mesenchymal stem cells facilitate corneal wound healing via regulating the p44/42 MAPK pathway. Graefes Arch Clin Exp Ophthalmol 261, 723–734 (2023). https://doi.org/10.1007/s00417-022-05956-4

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