A tissue-engineered endothelialized dermis to study the modulation of angiogenic and angiostatic molecules on capillary-like tube formation in vitro.
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.


OBJECTIVE
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 microg x 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.
Hudon
V
V
Laboratoire d'Organogenèse Expérimentale, Département de Chirurgie, Université Laval, CHA, Hôpital du Saint-Sacrement, 1050 Chemin Sainte-Foy, Québec, Canada, G1S 4L8.
Berthod
F
F
Black
A F
AF
Damour
O
O
Germain
L
L
Auger
F A
FA
D002196:Capillaries / Q000254:growth & development*; D016228:Endothelial Growth Factors / Q000502:physiology; D016222:Fibroblast Growth Factor 2; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D018613:Microscopy, Confocal / Q000379:methods; D018919:Neovascularization, Physiologic / Q000502:physiology; D012867:Skin / Q000098:blood supply*; D023822:Tissue Engineering / Q000379:methods*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2