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Successful grafting of tissue-engineered fetal skin

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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.

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References

  1. Atala AAJ (2014) Translational regenerative medicine, 1st edn. Academic Press, New York

  2. Adzick NS et al (2011) A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 364(11):993–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Johnson MP et al (2016) The management of myelomeningocele study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol

  4. Mazzone L et al (2014) Experimental tissue engineering of fetal skin. Pediatr Surg Int 30(12):1241–1247

    Article  CAS  PubMed  Google Scholar 

  5. Pontiggia L et al (2009) Markers to evaluate the quality and self-renewing potential of engineered human skin substitutes in vitro and after transplantation. J Invest Dermatol 129(2):480–490

    Article  CAS  PubMed  Google Scholar 

  6. Braziulis E et al (2012) Modified plastic compression of collagen hydrogels provides an ideal matrix for clinically applicable skin substitutes. Tissue Eng Part C Methods 18(6):464–474

    Article  CAS  PubMed  Google Scholar 

  7. Meuli M et al (1995) In utero surgery rescues neurological function at birth in sheep with spina bifida. Nat Med 1(4):342–347

    Article  CAS  PubMed  Google Scholar 

  8. Meuli M et al (2013) Premiere use of integra artificial skin to close an extensive fetal skin defect during open in utero repair of myelomeningocele. Pediatr Surg Int 29(12):1321–1326

    Article  PubMed  Google Scholar 

  9. Meuli M, Moehrlen U (2014) Fetal surgery for myelomeningocele is effective: a critical look at the whys. Pediatr Surg Int 30(7):689–697

    Article  PubMed  Google Scholar 

  10. Mangels KJ et al (2000) Use of bipedicular advancement flaps for intrauterine closure of myeloschisis. Pediatr Neurosurg 32(1):52–56

    Article  CAS  PubMed  Google Scholar 

  11. Moldenhauer JS et al (2015) Fetal myelomeningocele repair: the post-MOMS experience at the Children’s Hospital of Philadelphia. Fetal Diagn Ther 37(3):235–240

    Article  PubMed  Google Scholar 

  12. Mazzola CA et al (2002) Dermoid inclusion cysts and early spinal cord tethering after fetal surgery for myelomeningocele. N Engl J Med 347(4):256–259

    Article  PubMed  Google Scholar 

  13. Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6(4):328–340

    Article  CAS  PubMed  Google Scholar 

  14. Prunieras M, Regnier M, Woodley D (1983) Methods for cultivation of keratinocytes with an air–liquid interface. J Invest Dermatol 81(1 Suppl):28s–33s

    Article  CAS  PubMed  Google Scholar 

  15. Cartlidge P (2000) The epidermal barrier. Semin Neonatol 5(4):273–280

    Article  CAS  PubMed  Google Scholar 

  16. Evans NJ, Rutter N (1986) Development of the epidermis in the newborn. Biol Neonate 49(2):74–80

    Article  CAS  PubMed  Google Scholar 

  17. Burrington JD (1971) Wound healing in the fetal lamb. J Pediatr Surg 6(5):523–528

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank an anonymous private sponsor, the Gottfried and Julia Bangerter-Rhyner Foundation, and the Children’s Research Center of the University Children’s Hospital Zurich, Switzerland, for their generous financial support and interest in our work.

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Authors and Affiliations

  1. Department of Surgery, University Children’s Hospital Zurich, Zurich, Switzerland

    L. Mazzone, M. Pratsinis & M. Meuli

  2. Zurich Center for Fetal Diagnosis and Treatment, Zurich, Switzerland

    L. Mazzone & M. Meuli

  3. Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Zurich, Switzerland

    L. Mazzone, L. Pontiggia, E. Reichmann & M. Meuli

  4. Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland

    L. Mazzone, L. Pontiggia, E. Reichmann & M. Meuli

Authors
  1. L. Mazzone
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  2. M. Pratsinis
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  3. L. Pontiggia
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  4. E. Reichmann
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  5. M. Meuli
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Corresponding author

Correspondence to L. Mazzone.

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The authors declare that they have no conflict of interest.

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Mazzone, L., Pratsinis, M., Pontiggia, L. et al. Successful grafting of tissue-engineered fetal skin. Pediatr Surg Int 32, 1177–1182 (2016). https://doi.org/10.1007/s00383-016-3977-z

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  • DOI: https://doi.org/10.1007/s00383-016-3977-z

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