Differing responses of human follicular and nonfollicular scalp cells in an in vitro wound healing assay: Effects of estrogen on vascular endothelial growth factor secretion

Improved wound healing of hairy skin may involve mesenchymal hair follicle cells with stem cell potential and enhancement by estrogen therapy. How estrogen affects follicular dermal papilla (DP) and dermal sheath (DS) cells in wound healing is unknown. Therefore, a comparison of estradiol action on DP, DS, and corresponding interfollicular dermal fibroblasts (DF) in a scratch-wound assay was performed using matching primary cultures established from female temporo-occipital scalp. All three cell types expressed mRNA transcripts and protein for estrogen receptors alpha (ER alpha) and beta (ER beta). DF ER alpha transcripts were half that of DP and one-third of DS cells, while DF ER beta transcripts were two-thirds of DP and DS cells. In the scratch-wound assay all three cells types migrated at similar rates, but only the rate of DF was enhanced by estradiol. Mechanical wounding increased DNA synthesis rates of all three cell types and increased the secretion of collagen by DF and DS cells. All three secreted similar basal levels of vascular endothelial growth factor (VEGF), which was increased by wounding DF and DS cells, but not DP cells. DP cells required estradiol to increase VEGF secretion; by contrast VEGF secretion was decreased by estradiol in wounded DS cells. These results highlight differences in the responses of DF, DP, and DS cells to estradiol in a scratch-wound assay, providing further support for the dichotomy of cellular functions in the hair follicle. Further understanding of the role of estrogen in cutaneous wound healing may have important implications for the management of chronic wounds and scarring.