Dermal papilla cells cultured as spheres improve angiogenesis

Abstract

Tissue-engineeredskin represents a helpful strategy for the treatment of deep skininjuries. Nevertheless, these skin substitutes must promote and encourage propervascularization for a successful graft take. Previous work showed that dermal papillacells (DPC) favour an earlier neovascularization process of grafted skin substitute contributingto the rapid maturation of the neovascular network, reducing inflammationand favouring extracellular matrix remodelling in nude mice. Based on these results,we studied the influence of DPC and its culture conditions on the different stages ofangiogenesis in in vitro models. Here, we showed that DPC cultured as spheres favourthe expression of angiogenic factors such as VEGF, FGF2 and angiogenin comparedto their monolayer culture. To study the effects of DPC on the different stages ofangiogenesis, an in vitro model has been adapted. DPC cultured as spheres significantlyenhanced HUVEC migration and tubule formation, indicating the importanceof employing physiological culture systems that provide a closer representation ofcell behaviour and interactions occurring in vivo. Overall, these results allow us tospeculate that the use of DPC spheres in skin substitutes could promote its grafting,vascularization and vascular network maturation through the secretion of angiogenicfactors. This approach has great potential to improve clinical outcomes in regenerativemedicine and skin wound repair.