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Impact of human mesenchymal cells of different body site origins on the maturation of dermo-epidermal skin substitutes

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Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Aim of the study

The use of autologous bio-engineered dermo-epidermal skin substitutes (DESS) yields a pivotal opportunity to cover large skin defects in human patients. These skin grafts consist of both epidermal and dermal compartments necessary for robust and permanent functional wound closure. In this study, we investigated the impact of mesenchymal cells derived from different body site origins on the expression pattern of diverse markers within DESS.

Methods

Human keratinocytes were obtained from interfollicular epidermis, and mesenchymal cells were isolated from foreskin, palmar skin, fat tissue, and tonsils. After expansion, epidermal cells were seeded on collagen I hydrogels containing stromal cells. These human DESS were transplanted on the back of immune-incompetent rats. After 3 weeks, transplants were excised and analyzed using immunohistology techniques.

Main results

The macroscopic appearance of skin grafts containing tonsil, fat tissue, or palmar derived mesenchymal cells, was similar to substitutes with foreskin derived dermal fibroblasts. All skin grafts had a strong membrane-localized expression of Lingo-1 in the epidermis. Additionally, we observed an intense expression of transglutaminase 5 in upper epidermal cell layers of the skin grafts confirming a proper keratinocyte differentiation. Tropoelastin was localized throughout the dermal compartments and tightly in contact with the dermo-epidermal junction suggesting an advanced maturation of all skin grafts.

Conclusions

Our data implicate that stromal cells derived from tonsil, fat tissue, and palmar skin can assume fibroblast functions supporting keratinocyte proliferation and differentiation. These findings indicate that distinct types of mesenchymal cells can be clinically used for skin engineering purposes.

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Acknowledgements

This work was financially supported by the Clinical Research Priority Programs (CRPP) of the Faculty of Medicine of the University of Zurich. We are particularly grateful to the Gaydoul Foundation and the sponsors of “DonaTissue” (Thérèse Meier and Robert Zingg) for their generous financial support and interest in our work.

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Authors and Affiliations

  1. Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Katarzyna Michalak-Micka, Agnes S. Klar, Ernst Reichmann & Thomas Biedermann

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

    Katarzyna Michalak-Micka, Agnes S. Klar, Sophie Böttcher-Haberzeth, Ernst Reichmann, Martin Meuli & Thomas Biedermann

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

    Sophie Böttcher-Haberzeth & Martin Meuli

Authors
  1. Katarzyna Michalak-Micka
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  2. Agnes S. Klar
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  3. Sophie Böttcher-Haberzeth
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  4. Ernst Reichmann
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  5. Martin Meuli
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  6. Thomas Biedermann
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Corresponding author

Correspondence to Thomas Biedermann.

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Conflict of interest

ER and MM are co-founding members and shareholders of “Cutiss AG”, a company to fund the further development of the tissue-engineered skin substitutes. All other authors declare that they have no conflict of interest.

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Michalak-Micka, K., Klar, A.S., Böttcher-Haberzeth, S. et al. Impact of human mesenchymal cells of different body site origins on the maturation of dermo-epidermal skin substitutes. Pediatr Surg Int 35, 121–127 (2019). https://doi.org/10.1007/s00383-018-4383-5

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  • DOI: https://doi.org/10.1007/s00383-018-4383-5

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