title: Improved skin wound epithelialization by topical delivery of soluble factors from fibroblast aggregates.
abstract: BACKGROUND
  Timely coverage of an excised burn wound with a split-thickness skin graft, and efficient epithelialization at the donor site wound are key components in the treatment of burn patients. Prompt healing is dependent on paracrine support from underlying dermal connective tissue fibroblasts.
  
  
  OBJECTIVE
  Using the skin graft donor site in pig as a model for epithelialization, our aim was to evaluate if dermal signals, derived from cultured dermal fibroblast aggregates (Finectra), can promote epidermal regeneration.
  
  
  METHODS
  Partial-thickness skin wounds were made with a dermatome on the backs of three domestic pigs. After randomization, topical treatment was initiated by application of Finectra (n=6) or factors from standard fibroblast monolayer cultures (n=6) trapped in a slow-clotting fibrin matrix. Saline was applied to contralateral wounds to serve as corresponding untreated controls (n=12). After 3 days, full-thickness skin samples representing the whole wound area were obtained. Histological sections of these samples were analyzed for epithelialization, cell migration from lateral wound edges and hair follicles, as well as for formation of granulation tissue.
  
  
  RESULTS
  In response to topical delivery of Finectra, a significant acceleration of epithelialization (p<0.001) across the wound surface as well as from the wound edges was evident. Marked increase in thickness of granulation tissue (p<0.001) was noted in wounds treated with Finectra. Epihelialization originated from adnexal structures in which epithelial islets showed positive staining for cytokeratin-14 and PCNA.
  
  
  CONCLUSIONS
  These data show that the fibroblast aggregate-derived paracrine mediators, Finectra, stimulate epidermal regeneration in vivo.
authors: Institute of Biomedicine, Pharmacology, University of Helsinki, Finland. matti.peura@helsinki.fi
authors: Matti
authors: M
authors: Peura
authors: Ilkka
authors: I
authors: Kaartinen
authors: Sari
authors: S
authors: Suomela
authors: Mika
authors: M
authors: Hukkanen
authors: Jozef
authors: J
authors: Bizik
authors: Ari
authors: A
authors: Harjula
authors: Esko
authors: E
authors: Kankuri
authors: Jyrki
authors: J
authors: Vuola
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology / Q000627:therapeutic use*; D002056:Burns / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000737:chemistry*; D015603:Keratinocytes / Q000187:drug effects; D019899:Paracrine Communication / Q000502:physiology; D034421:Sus scrofa; D014945:Wound Healing / Q000502:physiology*
chemical_list: D001685:Biological Factors