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Paracrine effects of mesenchymal stem cells on the activation of keratocytes
  1. Zhixin Jiang1,2,3,
  2. Guangjie Liu4,
  3. Fanlan Meng1,
  4. Weiyi Wang5,
  5. Peng Hao1,2,3,
  6. Yang Xiang1,
  7. Yuchuan Wang1,2,3,
  8. RuiFang Han1,2,3,
  9. Fang Li2,
  10. Liming Wang1,2,3,
  11. Xuan Li1,2,3
  1. 1Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China
  2. 2Nankai University Eye Hospital, Tianjin, China
  3. 3Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China
  4. 4Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
  5. 5Department of Ophthalmology, Tianjin Huanhu Hospital, Tianjin, China
  1. Correspondence to Dr Xuan Li, Tianjin Eye Hospital 300020, Tianjin, China; xuanli08{at}


Aims The purpose of this study is to investigate the impact of mesenchymal stem cell (MSC)-derived soluble factors on the function of keratocytes, with a particular focus on the processes involved in wound healing, including keratocyte activation, migration and proliferation as well as extracellular matrix (ECM) synthesis.

Methods Primary cultured rabbit keratocytes were treated with MSC-conditioned medium (MSC-CM). The paracrine factors released by bone marrow MSCs were examined by ELISA. Time-lapse microscope was used to examine wound closure in vitro. Mouse model of corneal injury was made by epithelial scraping after ethanol injury.

Results MSC-CM significantly increased the wound closure rate of corneal stromal cells in vitro. This enhancement of wound closure by MSC-CM was due to the promotion of cell migration. MSC-CM enhanced keratocyte survival following ethanol injury via inhibiting apoptosis. The expression of ECM component genes in keratocytes was upregulated by MSC-CM. In addition, MSC-CM promoted corneal epithelial wound healing following chemical injury. A number of wound healing mediators were detected in MSC-CM, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGFβ1), interleukin 8 (IL8), interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1).

Conclusion MSC secretes certain factors that accelerate corneal re-epithelialisation. The paracrine effects of MSC on corneal wound healing including improvements in cell viability, migration and ECM formation.

  • wound healing
  • stem cells
  • cornea

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  • Contributors GL and XL wrote the manuscript. ZJ, GL, XL, FM, PH, YX, WW, RH, YW, LW and FL acquired the data. GL and XL analysed the data. All of the authors reviewed and edited the manuscript and gave final approval of the version to be published.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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