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Corneal Epithelial Stem Cell Study Highlights Dry Eye as a Major Obstacle to Corneal Epithelial Wound Healing

Review of “Different Effects of Pro‐Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

Adequate corneal epithelial wound healing mediated by corneal epithelial stem cells (CESCs) promotes the preservation of corneal transparency and vision by maintaining a healthy corneal epithelium. Persistent inflammation and hyperosmolarity (or dry eye) can induce damage to the eye surface and resident stem/progenitor cells and impede cell transplantation approaches [1]; however, we currently do not understand to what extent these two conditions affect CESC homeostasis and corneal epithelial wound healing.

In a new STEM CELLS Translational Medicine study, researchers from the group of Qingjun Zhou (Shandong Academy of Medical Sciences, Qingdao, China) now establish that while pro‐inflammatory cytokines transiently inhibit wound healing, hyperosmosis causes more severe damage leading to apoptosis or necrosis, thereby suggesting that the two conditions impact both CESCs and corneal epithelial wound healing in a considerably different manner [2]. Yang et al. anticipate that their findings will provide the cellular basis for the control of inflammation/dry eye before limbal stem cell transplantation.

Employing cells derived from both mouse [3, 4] and rabbit, the authors demonstrated that treatment with interleukin‐1 beta (IL‐1β) or tumor necrosis factor alpha (TNF‐α), to induce inflammation, or sodium chloride, to induce hyperosmotic stress, led to significant morphological changes in CESCs and decreased colony‐forming efficiency or colony‐forming size in vitro, suggesting a loss in stemness. Meanwhile, in vivo analysis discovered that hyperosmotic stress also more severely affected the inhibition of corneal epithelial wound healing in a mouse model. 

However, while CESCs recovered from pro‐inflammatory factor treatment well, hyperosmotic stress caused a more significant increase in apoptosis and necrosis, persistent cell cycle arrest in G2/M phase, more significant inhibition of corneal epithelial wound healing, and elevated levels of inflammatory factors, both in vitro and in vivo. Of note, the combination of both treatments further exacerbated the delay to epithelial repair and promoted significant levels of apoptosis. 

Overall, the authors of this new study highlight the importance of control over hyperosmotic stress to the health and wound healing capacity of the corneal epithelium, and hope that these findings will aid future approaches looking to optimize cell transplantation into the eye as well as other eye-focused regenerative therapies.

For more how stresses and strains can inhibit stem cell function, stay tuned to the Stem Cells Portal for more!


  1. Haagdorens M, Van Acker SI, Van Gerwen V, et al., Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies. Stem Cells International 2016;2016:9798374.
  2. Yang L, Zhang S, Duan H, et al., Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice. STEM CELLS Translational Medicine 2019;8:46-57.
  3. Zhou Q, Chen P, Di G, et al., Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing. STEM CELLS 2015;33:1566-76.
  4. Chen J, Chen P, Backman LJ, et al., Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt. Scientific Reports 2016;6:25870.