title: A novel three-dimensional model system for keloid study: organotypic multicellular scar model.
abstract: We developed a three-dimensional organotypic multicellular spheroid scar model to mimic the microenvironment of human keloid tissues. Keloid tissues were cultured for 7 days. Changes in total cellularity and apoptotic index in the primary keloid spheroid cultures were evaluated histologically and with a TUNEL assay, respectively. The expression profiles of transforming growth factor-β (TGF-β), collagen I, collagen III, elastin, fibronectin, matrix metalloproteinase-2, and matrix metalloproteinase-9 were examined with immunohistochemistry. In addition, these expression profiles were investigated after treating primary keloid spheroids with triamcinolone acetonide. Cell viability and morphology of ex vivo cultured keloid spheroids were maintained, and the apoptotic index did not increase for up to 1 week in culture. Keloid spheroids cultivated ex vivo retained the major characteristics of keloids, such as high levels of collagen I and TGF-β expression for up to 7 days. The biological activity of keloids responding to TGF-β was also maintained during ex vivo culture. Moreover, ex vivo triamcinolone acetonide treatment of cultivated keloid spheroids significantly reduced collagen I, collagen III, elastin, and fibronectin expression levels, in accordance with clinical observations. The three-dimensional organotypic multicellular spheroid keloid culture will allow investigators to study keloid pathogenesis and test potential keloid therapeutic agents.
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Jai
authors.initials: WJ
authors.lastname: Lee
authors.forename: Il-Kyu
authors.initials: IK
authors.lastname: Choi
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Yong Oock
authors.initials: YO
authors.lastname: Kim
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
mesh_terms: D002478:Cells, Cultured / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D007627:Keloid / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008954:Models, Biological; D018874:Spheroids, Cellular / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016212:Transforming Growth Factor beta; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9