Paracrine effects of mesenchymal stem cells on the activation of keratocytes

Br J Ophthalmol. 2017 Nov;101(11):1583-1590. doi: 10.1136/bjophthalmol-2016-310012. Epub 2017 Aug 26.

Abstract

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.

Keywords: cornea; stem cells; wound healing.

MeSH terms

  • Animals
  • Cell Survival
  • Cell- and Tissue-Based Therapy / methods*
  • Cells, Cultured
  • Corneal Injuries / metabolism*
  • Corneal Injuries / pathology
  • Corneal Injuries / therapy
  • Corneal Keratocytes / metabolism
  • Corneal Keratocytes / pathology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Rabbits
  • Wound Healing*