title: Bone marrow cells and CD117-positive haematopoietic stem cells promote corneal wound healing.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, University Erlangen-Nuremberg, Erlangen, Germany. saadettinsel@googlemail.com
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
authors.forename: Ulf M
authors.initials: UM
authors.lastname: Schilling
authors.forename: Norbert
authors.initials: N
authors.lastname: Nass
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.forename: Fabian
authors.initials: F
authors.lastname: Garreis
authors.forename: Matthias
authors.initials: M
authors.lastname: Knak
authors.forename: Joachim
authors.initials: J
authors.lastname: Storsberg
authors.forename: Maja
authors.initials: M
authors.lastname: Kaiser
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.forename: Dirk
authors.initials: D
authors.lastname: Ehrich
authors.forename: Timm
authors.initials: T
authors.lastname: Bredehorn-Mayr
authors.forename: Friedrich
authors.initials: F
authors.lastname: Paulsen
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002057:Burns, Chemical / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002469:Cell Separation; D002478:Cells, Cultured; D003320:Corneal Ulcer / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000502:physiology; D005126:Eye Burns / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018380:Hematopoietic Stem Cell Transplantation; D053551:Keratin-12 / Q000378:metabolism; D053558:Keratin-3 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012038:Regeneration; D012972:Sodium Hydroxide; D014945:Wound Healing / Q000502:physiology*
chemical_list: D053551:Keratin-12; D053558:Keratin-3; D012972:Sodium Hydroxide; D019009:Proto-Oncogene Proteins c-kit