Original Article

Subject Category: Wound Healing

Journal of Investigative Dermatology (2009) 129, 480–490; doi:10.1038/jid.2008.254; published online 21 August 2008

Markers to Evaluate the Quality and Self-Renewing Potential of Engineered Human Skin Substitutes In Vitro and after Transplantation

Luca Pontiggia1, Thomas Biedermann1, Martin Meuli1, Daniel Widmer1, Sophie Böttcher-Haberzeth1, Clemens Schiestl1, Jörg Schneider1, Erik Braziulis1, Irene Montaño1, Claudia Meuli-Simmen1,2 and Ernst Reichmann1

  1. 1Tissue Biology Research Unit, Department of Surgery, University Children's Hospital, Zurich, Switzerland
  2. 2Klinik für Plastische u. Wiederherstellungschirurgie, Kantonsspital, Tellstrasse, 5001 Aarau, Switzerland

Correspondence: PD, Dr. Ernst Reichmann, Tissue Biology Research Unit, Department of Surgery, University Children's Hospital, Steinwiesstrasse 75, Zurich CH-8032, Switzerland. E-mail: ernst.reichmann@kispi.uzh.ch

Received 7 August 2007; Revised 2 June 2008; Accepted 4 July 2008; Published online 21 August 2008.

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Abstract

We screened a series of antibodies for their exclusive binding to the human hair follicle bulge. In a second step these antibodies were to be used to identify basal keratinocytes and potential epithelial stem cells in the human epidermis and in engineered skin substitutes. Of all the antibodies screened, we identified only one, designated C8/144B, that exclusively recognized the hair follicle bulge. However, C8/144B-binding cells were never detected in the human epidermal stratum basale. In the bulge C8/144B-binding cells gave rise to cytokeratin 19-positive cells, which were also tracked in the outer root sheath between bulge and the hair follicle matrix. Remarkably, cytokeratin 19-expressing cells were never detected in the hair follicle infundibulum. Yet, cytokeratin 19-expressing keratinocytes were found in the epidermal stratum basale of normal skin as a subpopulation of cytokeratin 15-positive (not C8/144B-positive) basal keratinocytes. Cytokeratin 19/cytokeratin 15-positive keratinocytes decreased significantly with age. We suggest that cytokeratin 19-expressing cells represent a subpopulation of basal keratinocytes in neonates and young children (up to 1.5 years) that is particularly adapted to the lateral expansion of growing skin. Our data show that cytokeratin 19 in combination with cytokeratin 15 is an important marker to routinely monitor epidermal homeostasis and (at least indirectly) the self-renewing potential of engineered skin.

Abbreviations:

HF, hair follicle; K, cytokeratin; PBS, phosphate-buffered saline; SC, stem cell

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