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A tissue‐engineered endothelialized dermis to study the modulation of angiogenic and angiostatic molecules on capillary‐like tube formation in vitro
Author(s) -
Hudon V.,
Berthod F.,
Black A.F.,
Damour O.,
Germain L.,
Auger F.A.
Publication year - 2003
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2003.05298.x
Subject(s) - dermis , umbilical vein , angiogenesis , chemistry , dermal fibroblast , in vitro , basic fibroblast growth factor , fibroblast , endothelial stem cell , microbiology and biotechnology , biophysics , biomedical engineering , growth factor , anatomy , biology , medicine , biochemistry , cancer research , receptor
Summary Background Because angiogenesis is a major feature of different physiological and pathological situations, the identification of factors that stimulate or inhibit this process and the elucidation of their mechanisms of action are most certainly of clinical relevance. We have produced a new model of endothelialized reconstructed dermis that promotes the spontaneous formation of a human capillary‐like network and its stabilization in vitro for a period longer than 1 month. Objectives The aim of this work was to describe the three‐dimensional structure of the capillary‐like network. Thereafter we strove to study, quantitatively and qualitatively, the influence of angiogenic and angiostatic drugs on capillary‐like tube (CLT) formation in vitro in the model. Methods The endothelialized dermis was prepared by coculturing two human cell types, dermal fibroblasts and umbilical vein endothelial cells, in a collagen sponge biomaterial. Results The visualization by confocal microscopy of the tubes present in the model showed that the endothelial structures were not cord‐like but rather CLTs with well‐defined lumina. Moreover, these tubes were organized in a complex network of branching structures. When angiogenic factors (vascular endothelial growth factor 10 ng mL −1 or basic fibroblast growth factor 10 ng mL −1 ) were added to the model, 1·8 and 1·4 times more capillaries, respectively, were observed, whereas the addition of progesterone (10 μg mL −1 ) reduced by 2·4 times the number of tubes compared with the control. Conclusions These results suggest that this model is a highly efficient assay for the screening of potentially angiogenic and angiostatic compounds.