Deep and Superficial Keloid Fibroblasts Contribute Differentially to Tissue Phenotype in a Novel In Vivo Model of Keloid Scar

作者:Supp Dorothy M*; Hahn Jennifer M; Glaser Kathryn; McFarland Kevin L; Boyce Steven T
来源:Plastic and Reconstructive Surgery, 2012, 129(6): 1259-1271.
DOI:10.1097/PRS.0b013e31824ecaa9

摘要

Background: Keloids are thick fibrous scars that are refractory to treatment and unique to humans. The lack of keloid animal models has hampered development of effective therapies. The authors%26apos; goal was to develop an animal model of keloids using grafted engineered skin substitutes composed of keloid-derived cells. To demonstrate the model%26apos;s utility, differences between deep and superficial keloid fibroblasts were investigated. %26lt;br%26gt;Methods: Engineered skin substitutes were prepared using six combinations of cells: 1, normal keratinocytes and normal fibroblasts; 2, normal keratinocytes and deep keloid fibroblasts; 3, normal keratinocytes and superficial keloid fibroblasts; 4, keloid keratinocytes and normal fibroblasts; 5, keloid keratinocytes and deep keloid fibroblasts; and 6, keloid keratinocytes and superficial keloid fibroblasts. Engineered skin substitutes stably grafted to athymic mice were evaluated for wound area, thickness, and gene expression. %26lt;br%26gt;Results: Deep keloid fibroblasts displayed elevated expression of type 1 collagen alpha 1(COL1A1), transforming growth factor beta-1, periostin, plasminogen activator inhibitor 2, and inhibin beta A compared with superficial keloid fibroblasts and normal fibroblasts. After grafting, engineered skin substitutes in group 5 were significantly thicker than controls and had increased COL1A1 expression. Engineered skin substitutes in group 6 showed significantly increased area. Histologic analysis revealed abnormal collagen organization in engineered skin substitutes containing deep keloid fibroblasts or superficial keloid fibroblasts. %26lt;br%26gt;Conclusions: Aspects of the phenotypes of engineered skin substitutes prepared with keloid cells are analogous to thickening and spreading of human keloid scars. Therefore, use of keloid engineered skin substitutes is a valuable new tool for the study of keloid scarring. (Plast. Reconstr. Surg. 129: 1259, 2012.)

  • 出版日期2012-6