title: A three-dimensional skin equivalent reflecting some aspects of in vivo aged skin.
abstract: Human skin undergoes morphological, biochemical and functional modifications during the ageing process. This study was designed to produce a 3-dimensional (3D) skin equivalent in vitro reflecting some aspects of in vivo aged skin. Reconstructed skin was generated by co-culturing skin fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan scaffold, and ageing was induced by the exposition of fibroblasts to Mitomycin-C (MMC). Recently published data showed that MMC treatment resulted in a drug-induced accelerated senescence (DIAS) in human dermal fibroblast cultures. Next to established ageing markers, histological changes were analysed in comparison with in vivo aged skin. In aged epidermis, the filaggrin expression is reduced in vivo and in vitro. Furthermore, in dermal tissue, the amount of elastin and collagen is lowered in aged skin in vivo as well as after the treatment of 3D skin equivalents with MMC in vitro. Our results show histological signs and some aspects of ageing in a 3D skin equivalent in vitro, which mimics aged skin in vivo.
authors.affiliation: Institute of Biochemistry & Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.|Henkel AG & Co. KGaA, Düsseldorf, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Diekmann
authors.affiliation: Institute of Biochemistry & Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Lirija
authors.initials: L
authors.lastname: Alili
authors.affiliation: Institute of Biochemistry & Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.|Henkel AG & Co. KGaA, Düsseldorf, Germany.
authors.forename: Okka
authors.initials: O
authors.lastname: Scholz
authors.affiliation: Henkel AG & Co. KGaA, Düsseldorf, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Giesen
authors.affiliation: Henkel AG & Co. KGaA, Düsseldorf, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Holtkötter
authors.affiliation: Institute of Biochemistry & Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brenneisen
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D002648:Child; D048271:Chitosan / Q000737:chemistry; D018920:Coculture Techniques; D003094:Collagen / Q000737:chemistry; D004549:Elastin / Q000096:biosynthesis / Q000737:chemistry; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D000091344:Filaggrin Proteins; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D016685:Mitomycin / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D015595:Skin Aging; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006025:Glycosaminoglycans; D007381:Intermediate Filament Proteins; D016685:Mitomycin; D003094:Collagen; D004549:Elastin; D048271:Chitosan
keywords: Mitomycin-C; ageing; drug-induced accelerated senescence; reactive oxygen species; three-dimensional skin equivalent