title: Human amniotic fluid derived cells can competently substitute dermal fibroblasts in a tissue-engineered dermo-epidermal skin analog.
abstract: OBJECTIVE
  Human amniotic fluid comprises cells with high differentiation capacity, thus representing a potential cell source for skin tissue engineering. In this experimental study, we investigated the ability of human amniotic fluid derived cells to substitute dermal fibroblasts and support epidermis formation and stratification in a humanized animal model.
  
  
  METHODS
  Dermo-epidermal skin grafts with either amniocytes or with fibroblasts in the dermis were compared in a rat model. Full-thickness skin wounds on the back of immuno-incompetent rats were covered with skin grafts with (1) amniocytes in the dermis, (2) fibroblasts in the dermis, or, (3) acellular dermis. Grafts were excised 7 and 21 days post transplantation. Histology and immunofluorescence were performed to investigate epidermis formation, stratification, and expression of established skin markers.
  
  
  RESULTS
  The epidermis of skin grafts engineered with amniocytes showed near-normal anatomy, a continuous basal lamina, and a stratum corneum. Expression patterns for keratin 15, keratin 16, and Ki67 were similar to grafts with fibroblasts; keratin 1 expression was not yet fully established in all suprabasal cell layers, expression of keratin 19 was increased and not only restricted to the basal cell layer as seen in grafts with fibroblasts. In grafts with acellular dermis, keratinocytes did not survive.
  
  
  CONCLUSIONS
  Dermo-epidermal skin grafts with amniocytes show near-normal physiological behavior suggesting that amniocytes substitute fibroblast function to support the essential cross-talk between mesenchyme and epithelia needed for epidermal stratification. This novel finding has considerable implications regarding tissue engineering.
authors.affiliation: Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Hartmann-Fritsch
authors.forename: Nynke
authors.initials: N
authors.lastname: Hosper
authors.forename: Joachim
authors.initials: J
authors.lastname: Luginbühl
authors.forename: Thomas
authors.initials: T
authors.lastname: Biedermann
authors.forename: Ernst
authors.initials: E
authors.lastname: Reichmann
authors.forename: Martin
authors.initials: M
authors.lastname: Meuli
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D020405:Dermis; D004817:Epidermis; D005347:Fibroblasts; D006801:Humans; D051381:Rats; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*