title: Epidermal growth factor mediated healing in stem cell-derived vocal fold mucosa.
abstract: BACKGROUND
  The goal of vocal fold wound healing is the reconstitution of functional tissue, including a structurally and functionally intact epithelium. Mechanisms underlying reepithelialization in vocal folds are not known, although it is suspected that healing involves the interplay between several growth factors. We used a three-dimensional human embryonic stem cell-derived model of vocal fold mucosa to examine the effects of one growth factor, exogenous epidermal growth factor (EGF), on wound healing.
  
  
  METHODS
  A scratch wound was created in the in vitro model. Rate of wound healing, epidermal growth factor receptor (EGFR) activation, and cell proliferation after injury were analyzed with and without application of both exogenous EGF and an EGFR inhibitor, gefitinib.
  
  
  RESULTS
  Wound repair after injury was significantly hastened by application of exogenous EGF (13.3 μm/h, ± 2.63) compared with absence of exogenous EGF (7.1 μm/h ± 2.84), but inhibited with concurrent addition of Gefitinib (5.2 μm/h, ± 2.23), indicating that EGF mediates wound healing in an EGFR-dependent manner. Immunohistochemistry revealed that EGFR activation occurred only in the presence of exogenous EGF. Although not statistically significant, increased density of Ki67 staining in the epithelium adjacent to the scratch wound was observed after treatment with EGF, suggesting a tendency for exogenous EGF to increase epithelial cell proliferation.
  
  
  CONCLUSIONS
  Exogenous EGF increases the rate of wound healing in an EGFR-dependent manner in a three-dimensional stem cell-derived model of vocal fold mucosa. This model of wound healing can be used to gain insight into the mechanisms that regulate vocal fold epithelial repair after injury.
authors.affiliation: School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Liliana
authors.initials: L
authors.lastname: Palencia
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Amritava
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Palecek
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin. Electronic address: thibeault@surgery.wisc.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Thibeault
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Ciara
authors.initials: C
authors.lastname: Leydon
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053595:Embryonic Stem Cells; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007820:Laryngeal Mucosa / Q000187:drug effects / Q000293:injuries* / Q000502:physiology; D014827:Vocal Cords / Q000187:drug effects / Q000293:injuries* / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D015415:Biomarkers; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: Epidermal growth factor; Epidermal growth factor receptor; Epithelium; Scratch assay; Vocal fold; Wound healing
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