title: Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.
abstract: BACKGROUND
  The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated.
  
  
  METHODS
  Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting. This enriched epithelial stem cell population was then transplanted by means of local injection into wound beds on the dorsum of nude mice. Viability, migration, healing, the development of nascent hair follicles, and gene and proteomic expression studies were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem cells enhanced healing when compared with controls.
  
  
  RESULTS
  Wound beds receiving LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle growth; and augmentation of the Wnt, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor pathways when compared with controls.
  
  
  CONCLUSIONS
  The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell–based therapy for the repair of full-thickness wounds and hair regeneration. These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.
authors.affiliation: Springfield, Ill.; and Baltimore, Md. From the Department of Surgery, Institute for Plastic Surgery, Microsurgery and Tissue Engineering Laboratory, Southern Illinois University; and the Departments of Plastic Surgery and Biological Chemistry, The Johns Hopkins University Hospital.
authors.forename: Denver M
authors.initials: DM
authors.lastname: Lough
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Anthony
authors.initials: A
authors.lastname: Blum
authors.forename: Joel D
authors.initials: JD
authors.lastname: Reichensperger
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Cosenza
authors.forename: Nathan
authors.initials: N
authors.lastname: Wetter
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cox
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Harrison
authors.forename: Michael W
authors.initials: MW
authors.lastname: Neumeister
mesh_terms: D000818:Animals; D002056:Burns / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology; D018859:Hair Follicle / Q000254:growth & development / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000378:metabolism; D012867:Skin / Q000293:injuries* / Q000503:physiopathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
chemical_list: C548022:Lgr6 protein, mouse; D043562:Receptors, G-Protein-Coupled