While vasculature plays an essential role in skin physiology its architecture and function are altered in aged and diseased skin. There is thus a need to develop innovative 3D in vitro models with adjustable vasculature to study the regulation of skin angiogenesis. Hence, this work aims to develop a vascularized skin model and study its characteristics in response to angiogenic stimuli. To do so, a scaffold-free approach was used: skin primary fibroblast cell sheets were generated and seeded with endothelial cells and human keratinocytes, in presence of Vascular Endothelial Growth Factor (VEGF). To assess the plasticity of the vasculature, the concentration of VEGF was decreased at the beginning of the reconstruction and/or after superimposition of cell sheets. Influence of VEGF modulation was analyzed at two main levels: (1) the vascular network (length ramification and recruitment of perivascular cells were visualized by CD31 and colIagen IV staining) and (2) the epidermal-dermal crosstalk (deposition of dermal-epidermal junction was analyzed by staining of collagen VII and laminin 332). Results showed that a decrease of VEGF at the beginning of the reconstruction only led to slight modifications of vascular network formation while absence of VEGF after superimposition of sheets drastically reduced vessel ramification throughout the sample depth. Recruitment of perivascular cells was reduced in response to VEGF decrease, regardless of the culture step. Interestingly, collagen VII and laminin 332 were inversely regulated, suggesting a disruption of DEJ maturation and highlighting the importance of compartment crosstalk. We have thus developed a novel and tunable vascularized skin model responding to subtle angiogenic stimuli. This model is of interest to mimic physiological and compromised skin conditions involving the vascular component.

ESDR607 - A new vascularized skin model responding to angiogenic stimuli

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.