De novo formation of human sebaceous glands using self-assembled skin substitutes

Sebaceous glands (SGs) contribute to skin physiology by producing sebum, which forms a lipid barrier preventing dehydration. Various skin conditions, including acne vulgaris and seborrheic dermatitis, are linked to their dysfunction. Several questions remain concerning the formation and regulation of these glands because there are few human tridimensional models available to address them. In this study, we investigated the conditions that allow SG formation in human tissue-engineered skin substitutes. We tested whether the source of epithelial cells, fibroblasts, and the extracellular environment influence the SG formation in vitro and after grafting onto mice. Our results showed that SGs formed in substitutes produced with epithelial cells derived from scalp but were absent in those generated from foreskin or breast skin tissues, whereas the fibroblast origin did not affect this process. However, no SG was found in substitutes produced from decellularized dermal matrices that were recellularized with fibroblasts and scalp epithelial cells, suggesting that some extracellular cues lost after decellularization play a major role in SG formation. Our work establishes an unprecedented model to study human SG formation and function and will likely be instrumental to investigate the pathogenesis of various diseases of the SG in the future.