Therapeutic Effects of Lyophilized Conditioned-Medium Derived from Corneal Mesenchymal Stromal Cells on Corneal Epithelial Wound Healing

Curr Eye Res. 2020 Dec;45(12):1490-1496. doi: 10.1080/02713683.2020.1762227. Epub 2020 May 14.

Abstract

Objectives: The conditioned-medium derived from corneal mesenchymal stromal cells (cMSCs) has been shown to have wound healing and immunomodulatory effects in corneal injury models. Here, the therapeutic effects of lyophilized cMSC conditioned-medium were compared with fresh conditioned-medium. Methods: The epithelial wound healing effects of fresh and lyophilized cMSC conditioned-medium were compared with conditioned-medium from non-MSC cells (corneal epithelial cells) using scratch assay. To evaluate the anti-inflammatory effects of fresh and lyophilized cMSC conditioned-media, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the conditioned-media and measuring the expression of inflammatory genes. In vivo wound healing effects of fresh and lyophilized cMSC conditioned-media were assessed in a murine model of cornea epithelial injury. Results: Both fresh and lyophilized cMSCs-derived conditioned-medium induced significantly faster closure of in vitro epithelial wounds compared to conditioned-medium from non-MSC cells (P < .0001). Treating stimulated macrophages with fresh or lyophilized cMSCs-derived conditioned-media significantly decreased the expression of inflammatory genes compared to control (P < .0001). Murine corneal epithelial wounds were healed by 87.6 ± 2.7% and 86.2 ± 4.6% following treatment with fresh and lyophilized cMSC conditioned-media, respectively, while the control was healed by 64.7 ± 16.8% (P < .05). Conclusion: Lyophilized cMSC-derived conditioned-medium is as effective as fresh conditioned-medium in promoting wound healing and modulating inflammation. The results of this study support the application of lyophilized cMSCs-derived conditioned-medium, which allows for more extended storage, as a promising non-invasive option in the treatment of corneal wounds.

Keywords: Human cornea; conditioned media; conditioned-medium; lyophilization; mesenchymal stromal cell; wound healing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corneal Injuries / metabolism
  • Corneal Injuries / physiopathology
  • Corneal Injuries / therapy*
  • Culture Media, Conditioned*
  • Epithelium, Corneal / injuries*
  • Epithelium, Corneal / physiology
  • Freeze Drying
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Limbus Corneae / cytology*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Stem Cell Transplantation*
  • Toll-Like Receptor 3 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing / physiology*

Substances

  • Culture Media, Conditioned
  • Interleukin-6
  • Interleukin-8
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Intercellular Adhesion Molecule-1