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Open Access 01-12-2018 | Original Paper

Reconstructed human keloid models show heterogeneity within keloid scars

Authors: Grace C. Limandjaja, Leonarda J. van den Broek, Taco Waaijman, Melanie Breetveld, Stan Monstrey, Rik J. Scheper, Frank B. Niessen, Susan Gibbs

Published in: Archives of Dermatological Research | Issue 10/2018

Abstract

Keloid scars are often described as having an actively growing peripheral margin with a regressing centre. The aim of this study was to examine the possible heterogeneity within keloids and the involvement of different regions within and around keloid scars in the pathogenesis, using an in vitro keloid scar model. In vitro skin models were constructed from keratinocytes and fibroblasts from normal skin and different regions within and around keloid scars: periphery, centre, and (adjacent) surrounding-normal-skin regions. Additionally, fibroblasts were isolated from the superficial-central and deep-central regions of the keloid and combined with central keratinocytes. All keloid regions showed increased contraction compared to normal skin models, particularly in central regions. Myofibroblasts were present in all keloid regions but were more abundant in models containing central-deep keloid fibroblasts. Secretion of anti-fibrotic HGF and extracellular matrix collagen IV gene expression was reduced in the central deep keloid compared to normal skin. No significant differences between peripheral and central regions within keloids were observed for inflammatory cytokine CCL20, CCL27, CXCL8, IL-6 and IL-18 secretion. Parameters for surrounding-normal-skin showed similarities to both non-lesional normal skin and keloids. In conclusion, a simple but elegant method of culturing keloid-derived keratinocytes and fibroblasts in an organotypic 3D scar model was developed, for the dual purpose of studying the underlying pathology and ultimately testing new therapeutics. In this study, these tissue engineered scar models show that the central keloid region shows a more aggressive keloid scar phenotype than the periphery and that the surrounding-normal-skin also shares certain abnormalities characteristic for keloids.

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Title: Reconstructed human keloid models show heterogeneity within keloid scars
Authors: Grace C. Limandjaja
Leonarda J. van den Broek
Taco Waaijman
Melanie Breetveld
Stan Monstrey
Rik J. Scheper
Frank B. Niessen
Susan Gibbs
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Archives of Dermatological Research / Issue 10/2018
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-018-1873-1

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Reconstructed human keloid models show heterogeneity within keloid scars

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