ArticleFrontiers in toxicology2026
From sebocytes to skin engineering human sebaceous organoids within a reconstructed dermal matrix.
Article in Frontiers in toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Sebaceous gland biology depends on the integration of lipid metabolism, tissue architecture, and stromal interactions, yet most available Methods: Using SZ95 sebocytes, we first established baseline responses in monolayer conditions using linoleic acid (LA) stimulation and pharmacological inhibition with retinol (RTN) and capsaicin (CPS). We then reconstructed a 3D organoid model in which a sebocyte-rich lipidogenic compartment was spatially organized within a matrix-supported microenvironment and associated with an outer stromal-like component. The model was evaluated using morphological, ultrastructural, and immunofluorescence analyses. To further define the mode of action of sebogenic activation in 3D, we analyzed genes related to extracellular matrix remodeling and tissue adaptation. Results: In both monolayer and 3D models, LA successfully induced a sebogenic program, characterized by increased lipid accumulation and upregulation of PPARγ and FABP4, which was effectively attenuated by RTN and CPS. The 3D model successfully maintained essential compartmentalization, epithelial identity, and stromal organization. Furthermore, transcriptional analysis revealed that LA stimulation in 3D induced coordinated changes in extracellular matrix and basement membrane genes (including MMP13, MMP16, and THBS2), indicating that sebogenesis is directly coupled with structural remodeling and microenvironmental adaptation. Conclusion: Altogether, these results demonstrate that we successfully reconstructed a functional
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