Dermal papilla cells cultured as spheres improve angiogenesis.

Tissue-engineered skin represents a helpful strategy for the treatment of deep skin injuries. Nevertheless, these skin substitutes must promote and encourage proper vascularization for a successful graft take. Previous work showed that dermal papilla cells (DPC) favour an earlier neovascularization process of grafted skin substitute contributing to the rapid maturation of the neovascular network, reducing inflammation and 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 of angiogenesis in in vitro models. Here, we showed that DPC cultured as spheres favour the expression of angiogenic factors such as VEGF, FGF2 and angiogenin compared to their monolayer culture. To study the effects of DPC on the different stages of angiogenesis, an in vitro model has been adapted. DPC cultured as spheres significantly enhanced HUVEC migration and tubule formation, indicating the importance of employing physiological culture systems that provide a closer representation of cell behaviour and interactions occurring in vivo. Overall, these results allow us to speculate that the use of DPC spheres in skin substitutes could promote its grafting, vascularization and vascular network maturation through the secretion of angiogenic factors. This approach has great potential to improve clinical outcomes in regenerative medicine and skin wound repair.

Androgens downregulate BMP2 impairing the inductive role of dermal papilla cells on hair follicle stem cells differentiation.

Hair follicle cyclical regeneration is regulated by epithelial-mesenchymal interactions. During androgenetic alopecia (AGA), hair follicle stem cells (HFSC) differentiation is impaired by deregulation of dermal papilla cells (DPC) secreted factors. We analyzed androgen influence on BMPs expression in DPC and their effect on HFSC differentiation to hair lineage. Androgens downregulated BMP2 and BMP4 in DPC spheroids. Addition of BMP2 restored alkaline phosphatase activity, marker of hair-inductivity in DPC, and DPC-induced HFSC differentiation, both inhibited by androgens. Concomitantly, in differentiating HFSC, an upregulation of BMPRIa and BMPRII receptors and nuclear ß-catenin accumulation, indicative of Wnt/ß-catenin pathway activation, were detected. Our results present BMP2 as an androgen-downregulated paracrine factor that contributes to DPC inductivity and favors DPC-induced HFSC differentiation to hair lineage, possibly through a crosstalk with Wnt/ß-catenin pathway. A comprehensive understanding of androgen-deregulated DPC factors and their effects on differentiating HFSC would help to improve treatments for AGA.