Bone marrow cells and CD117-positive haematopoietic stem cells promote corneal wound healing

Acta Ophthalmol. 2012 Aug;90(5):e367-73. doi: 10.1111/j.1755-3768.2012.02388.x. Epub 2012 Apr 20.

Abstract

Purpose: The present study was conducted to evaluate the therapeutic effects of topically applied bone marrow (BM) cells and CD117-positive haematopoietic stem (CD117(+)) cells on alkali-induced corneal ulcers.

Methods: Bone marrow cells and CD117(+) cells were isolated from syngenic mice and labelled with an intracellular cell tracer. Defined corneal wounds were produced in 89 eyes of syngenic mice and allowed to partially heal in vivo for 6 hr. The alkali-burned eyes were enucleated 6 hr postinjury and randomly divided into three groups. Control group (33 eyes) was incubated with medium only. The treatment groups received either BM cells (30 eyes) or CD117(+) cells (26 eyes) suspended in medium. Re-epithelialization process of corneal defects was qualitatively and quantitatively assessed and statistically analysed. The corneas were examined by histological and immunohistochemical methods.

Results: We found that the re-epithelialization of corneal wounds in both treatment groups was significantly accelerated as compared to the control group. During the follow-up period (85 hr), the corneal transparency was comparable in all groups. Morphological investigations of corneas from control and treatment group showed no evident differences in the phenotype of the regenerated epithelium. Additionally, corneas in the treatment groups were devoid of donor-derived BM cells and CD117(+) cells, respectively.

Conclusions: This study provides evidence that topical application of BM cells or CD117(+) cells can be used to reconstruct corneal surfaces. Because neither BM cells nor CD117(+) cells were integrated into the corneal epithelium, we suggest that soluble factors could be responsible for the positive effect of BM cells and CD117(+) cells on corneal wound healing.

MeSH terms

  • Animals
  • Bone Marrow Transplantation*
  • Burns, Chemical / metabolism
  • Burns, Chemical / pathology
  • Burns, Chemical / therapy*
  • Cell Separation
  • Cells, Cultured
  • Corneal Ulcer / metabolism
  • Corneal Ulcer / pathology
  • Corneal Ulcer / therapy*
  • Disease Models, Animal
  • Epithelium, Corneal / physiology
  • Eye Burns / chemically induced*
  • Eye Burns / metabolism
  • Eye Burns / pathology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Hematopoietic Stem Cell Transplantation*
  • Keratin-12 / metabolism
  • Keratin-3 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Organ Culture Techniques
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Regeneration
  • Sodium Hydroxide
  • Wound Healing / physiology*

Substances

  • Keratin-12
  • Keratin-3
  • Sodium Hydroxide
  • Proto-Oncogene Proteins c-kit