title: Successful grafting of tissue-engineered fetal skin.
abstract: OBJECTIVE
  Fetal repair of spina bifida results in improved outcomes and has therefore become a standard clinical procedure in some highly specialized centers. However, optimization of the procedure technique and timing is needed. Both might be achieved by facilitating the procedure using laboratory-grown fetal skin substitutes. The aim of this study was therefore to test in vivo the suitability of such a fetal skin substitute for an in utero application.
  
  
  METHODS
  Collagen-based hydrogels containing fetal ovine fibroblasts were seeded with fetal ovine keratinocytes and transplanted on immuno-incompetent nu/nu rats. After 3 weeks, grafts were harvested and analyzed histologically and by immunohistochemistry.
  
  
  RESULTS
  Laboratory-grown fetal ovine dermo-epidermal skin substitutes showed successful engraftment at 3 weeks. Histologically, grafts revealed a neo-dermis populated by fibroblasts and with ingrowth of vessels, and an epidermis with an adult-like, mature appearance depicting clearly basal, spinous, granular, and a corneal layer. Immunostaining confirmed a physiologically organized epidermis.
  
  
  CONCLUSIONS
  Fetal dermo-epidermal skin substitutes of ovine origin can successfully be grafted in vivo. In a next step, we will have to test whether favorable results can also be obtained when grafts are used in utero. If so, then human fetal spina bifida repair using laboratory-grown autologous fetal skin for defect closure may be envisaged.
authors.affiliation: Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch.|Zurich Center for Fetal Diagnosis and Treatment, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch.|Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch.|Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch.
authors.forename: L
authors.initials: L
authors.lastname: Mazzone
authors.affiliation: Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Pratsinis
authors.affiliation: Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland.|Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Pontiggia
authors.affiliation: Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland.|Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Reichmann
authors.affiliation: Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland.|Zurich Center for Fetal Diagnosis and Treatment, Zurich, Switzerland.|Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland.|Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Meuli
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D005333:Fetus / Q000601:surgery; D020100:Hydrogels; D015603:Keratinocytes / Q000637:transplantation; D023421:Models, Animal; D051381:Rats; D012756:Sheep; D016038:Skin Transplantation / Q000379:methods*; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020100:Hydrogels; D003094:Collagen
keywords: Fetal; Myelomeningocele; Skin; Spina bifida; Tissue engineering