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Transglutaminases, involucrin, and loricrin as markers of epidermal differentiation in skin substitutes derived from human sweat gland cells

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Abstract

Background/Purpose

In a multi-project research line, we are currently testing whether a morphologically and functionally near normal epidermis can be cultured from human sweat gland (SG) cells and be used as a skin substitute. The present study focuses on the stratum corneum of the epidermis that assumes a vital barrier function for the skin. The main process in the formation of the cornified cell envelope in human epidermis, i.e. crosslinking of proteins and lipids, is catalyzed by several transglutaminases (TG). Therefore, we compared the expression patterns of various TG and their substrates in SG-derived versus keratinocyte-derived epidermal substitutes.

Methods

Sweat gland cells, keratinocytes, and fibroblasts were isolated from human skin samples and cultivated separately to generate epidermal substitutes. These were transplanted onto the back of athymic rats. After 2 weeks, the transplants were excised and analyzed histologically as well as by indirect immunofluorescence. We looked at the expression of TG1, 3, 5, and their substrates involucrin and loricrin (=markers of epidermal differentiation) in SG-derived and keratinocyte-derived skin substitutes as well as in normal skin.

Results

The SG cell-derived epidermis was near normal anatomically, formed a cornified cell envelope and demonstrated TG1, 3, and 5 as well as involucrin and loricrin expression patterns similar to those found in keratinocyte-derived epidermis and normal control skin.

Conclusion

These findings support the thesis that SG cells have the potential to form a near normal stratified epidermal analog that might be used as a skin substitute. The expression of TG1 and 3, not normally expressed in human SG, suggests the presence of re-programmed SG cells and/or stem cells capable of both de novo generating and maintaining an epidermis.

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Acknowledgments

This work was supported by a grant from the European Union (EuroSTEC: LSHB-CT-2006-037409) and by the University of Zurich. We are particularly grateful to the Fondation Gaydoul and the sponsors of “DonaTissue” (Thérèse Meier, Robert Zingg, the Vontobel Foundation, and the Werner Spross Foundation) for their generous financial support and interest in our work.

Conflict of interest statement

The authors declare that none of them have any conflict of interest.

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Authors and Affiliations

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

    Sasha Tharakan, Luca Pontiggia, Thomas Biedermann, Sophie Böttcher-Haberzeth, Clemens Schiestl, Ernst Reichmann & Martin Meuli

  2. Department of Surgery, University Children’s Hospital, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Martin Meuli

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  1. Sasha Tharakan
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  2. Luca Pontiggia
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  3. Thomas Biedermann
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  4. Sophie Böttcher-Haberzeth
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  5. Clemens Schiestl
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  6. Ernst Reichmann
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  7. Martin Meuli
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Correspondence to Martin Meuli.

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Tharakan, S., Pontiggia, L., Biedermann, T. et al. Transglutaminases, involucrin, and loricrin as markers of epidermal differentiation in skin substitutes derived from human sweat gland cells. Pediatr Surg Int 26, 71–77 (2010). https://doi.org/10.1007/s00383-009-2517-5

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  • DOI: https://doi.org/10.1007/s00383-009-2517-5

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