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Human amniotic fluid derived cells can competently substitute dermal fibroblasts in a tissue-engineered dermo-epidermal skin analog

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Abstract

Purpose

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.

Conclusion

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.

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Acknowledgments

This work was financially supported by the EU-FP6 project EuroSTEC (soft tissue engineering for congenital birth defects in children: contract: LSHB-CT-2006-037409), by the EU-FP7 project EuroSkinGraft (FP7/2007-2013: grant agreement n° 279024), and by the University of Zurich. We are particularly grateful to the Fondation Gaydoul and the sponsors of “DonaTissue” (Thérèse Meier and Robert Zingg) for their generous financial support and interest in our work.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Fabienne Hartmann-Fritsch, Joachim Luginbühl, Thomas Biedermann & Ernst Reichmann

  2. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Nynke Hosper

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

    Martin Meuli

  4. Department of Surgery, Pediatric Burn Center, Plastic and Reconstructive Surgery, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Martin Meuli

Authors
  1. Fabienne Hartmann-Fritsch
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  2. Nynke Hosper
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  3. Joachim Luginbühl
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  4. Thomas Biedermann
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  5. Ernst Reichmann
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  6. Martin Meuli
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Corresponding author

Correspondence to Martin Meuli.

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Hartmann-Fritsch, F., Hosper, N., Luginbühl, J. et al. Human amniotic fluid derived cells can competently substitute dermal fibroblasts in a tissue-engineered dermo-epidermal skin analog. Pediatr Surg Int 29, 61–69 (2013). https://doi.org/10.1007/s00383-012-3207-2

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  • DOI: https://doi.org/10.1007/s00383-012-3207-2

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