An ex vivo model employing keloid-derived cell-seeded collagen sponges for therapy development

Abstract

The most distinctive feature of keloid is the extreme deposition of extracellular matrix, including collagens and proteoglycans (PGs). The focus of this study was the PG versican, which presumably defines keloid volume because of its ability to retain large amounts of water through its component glycosaminoglycans (GAGs). The excessive deposition of versican in keloids was examined by immunohistochemical analysis and by upregulation of the versican gene in these lesions by real-time PCR. The latter showed that mesenchymal cells derived from keloid lesion (KL) cells continue to exhibit above-normal versican production in culture. To establish a model of GAG deposition in keloids, collagen sponges seeded with KL cells (KL-SPos) were implanted in the subcutaneous space of nude mice. After 1 month, the KL-SPos were significantly heavier than the fibroblast (Fb)-seeded sponges (Fb-SPos). This ex vivo model was subsequently used to examine an inhibitory ability of IL-1β that was identified to reduce versican in vitro. IL-1β or chondroitinase ABC, when injected directly, successfully reduced the weight of the KL-SPos. Thus, on the basis of the change in weight of the seeded sponges, this ex vivo model can be used to test therapies aimed at reducing or inhibiting keloid formation and to study the pathogenesis of this aberrant response. © 2013 The Society for Investigative Dermatology.