New insights into induction of early-stage neovascularization in an improved tissue-engineered model of psoriasis.
We have previously shown that putrescine induces a psoriatic phenotype in tissue-engineered skin. The initial aim of this study was to further develop this in vitro model by introducing endothelial cells to mimic the increased vascularization found in psoriasis. Human keratinocytes and fibroblasts, which did not express CD34 or CD31 in 2D culture, were added to de-epidermised acellular human dermis and cultured for 4 weeks. For induction of a psoriatic phenotype, putrescine was added during this period. We report that after 4 weeks of culture, and particularly when exposed to putrescine, this model showed expression of vertically organised clusters of CD31 positive cells in the dermis in the absence of any exogenous endothelial cells. Further investigation in 2D cell cultures showed an indirect effect of putrescine on normal keratinocytes causing them to produce soluble factors that increased expression of CD133, CD34 and CD31 in cultured human dermal fibroblasts, previously negative for these antigens. This study reports a new and improved model of psoriasis for in vitro studies and offers a new insight into early stage neovascularization, which is of relevance not only to psoriasis, but to tissue engineering and wound healing in general.
Krajewska
Emilia
E
Department of Engineering Materials, Kroto Research Institute, University of Sheffield, Broad Lane, Sheffield, S3 7HQ, UK.
Lewis
Claire
C
Staton
Carolyn
C
MacGowan
Alice
A
MacNeil
Sheila
S
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D003470:Culture Media / Q000494:pharmacology; D020405:Dermis / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D004817:Epidermis / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D018919:Neovascularization, Physiologic; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011565:Psoriasis / Q000503:physiopathology*; D012867:Skin / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D003470:Culture Media; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1