title: 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.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yagi
authors.forename: Eri
authors.initials: E
authors.lastname: Muroga
authors.forename: Motoko
authors.initials: M
authors.lastname: Naitoh
authors.forename: Zenzo
authors.initials: Z
authors.lastname: Isogai
authors.forename: Seiya
authors.initials: S
authors.lastname: Matsui
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Utani
mesh_terms: D000328:Adult; D000818:Animals; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000637:transplantation; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007627:Keloid / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D061251:Primary Cell Culture; D015503:Surgical Sponges; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D053675:Versicans / Q000235:genetics* / Q000378:metabolism*
chemical_list: D006025:Glycosaminoglycans; D053583:Interleukin-1beta; C508322:VCAN protein, human; C508323:Vcan protein, mouse; D053675:Versicans; D019765:Chondroitin ABC Lyase