L Mazzone1,2,3,4, M Pratsinis5, L Pontiggia6,7, E Reichmann6,7, M Meuli5,8,6,7. 1. Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch. 2. Zurich Center for Fetal Diagnosis and Treatment, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch. 3. Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch. 4. Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. luca.mazzone@kispi.uzh.ch. 5. Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland. 6. Tissue Biology Research Unit, Department of Surgery, University Children's Hospital Zurich, Zurich, Switzerland. 7. Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. 8. Zurich Center for Fetal Diagnosis and Treatment, Zurich, Switzerland.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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: Mark P Johnson; Kelly A Bennett; Larry Rand; Pamela K Burrows; Elizabeth A Thom; Lori J Howell; Jody A Farrell; Mary E Dabrowiak; John W Brock; Diana L Farmer; N Scott Adzick Journal: Am J Obstet Gynecol Date: 2016-08-02 Impact factor: 8.661
Authors: M Meuli; C Meuli-Simmen; G M Hutchins; C D Yingling; K M Hoffman; M R Harrison; N S Adzick Journal: Nat Med Date: 1995-04 Impact factor: 53.440
Authors: Julie S Moldenhauer; Shelly Soni; Natalie E Rintoul; Susan S Spinner; Nahla Khalek; Juan Martinez-Poyer; Alan W Flake; Holly L Hedrick; William H Peranteau; Norma Rendon; Jamie Koh; Lori J Howell; Gregory G Heuer; Leslie N Sutton; Mark P Johnson; N Scott Adzick Journal: Fetal Diagn Ther Date: 2014-08-15 Impact factor: 2.587
Authors: N Scott Adzick; Elizabeth A Thom; Catherine Y Spong; John W Brock; Pamela K Burrows; Mark P Johnson; Lori J Howell; Jody A Farrell; Mary E Dabrowiak; Leslie N Sutton; Nalin Gupta; Noel B Tulipan; Mary E D'Alton; Diana L Farmer Journal: N Engl J Med Date: 2011-02-09 Impact factor: 91.245
Authors: Luca Pontiggia; Thomas Biedermann; Martin Meuli; Daniel Widmer; Sophie Böttcher-Haberzeth; Clemens Schiestl; Jörg Schneider; Erik Braziulis; Irene Montaño; Claudia Meuli-Simmen; Ernst Reichmann Journal: J Invest Dermatol Date: 2008-08-21 Impact factor: 8.551