Acne is a common skin disease that affects an estimated 650M people worldwide. While multiple factors are involved in acne pathogenesis, excess sebum secretion and inflammatory tissue cascade are considered key ones. Arachidonic acid (AA) is a derivative of linoleic acid, an omega-6 polyunsaturated fatty acid common in western diet. Eicosanoid metabolites originating from the AA cascade have been shown to induce sebogenesis through PPAR signaling, while also leading to inflammatory responses of sebaceous glands. Using sebocytes derived from human pluripotent stem cells (hiPSC), we developed an in-vitro assay for ingredient discovery or testing based on AA stimulation, and quantification of sebum production as well as proinflammatory cytokine secretion.
hiPSC-derived sebocytes (PCi-SEB, Phenocell) were thawed and cultured on fibronectine in sebocyte culture medium (PhenoCULT-SEB). Cells were challenged with AA after 3 days of culture, stained with BODIPY and analyzed by automated imaging for lipid content, while qPCR and ELISA were performed to quantify the proinflammatory cytokine response.
Following AA stimulation, sebocytes displayed prominent lipid droplet accumulation in the cytoplasm, with lipid staining increasing by about 10 folds compared to controls. The addition of 13-cis-retinoic acid to AA treated cells induced a 50% decrease in lipid production, compared to AA treated samples. Analysis by qPCR indicated a strong and significant up-regulation, at the mRNA levels, of the proinflammatory cytokines IL-6, IL-8 and TNF-α. Importantly, this pattern was inhibited in the presence of 13-cis-retinoic acid. Finally, IL-8 secretion in the supernatant was sharply increased in the presence of AA, while significantly diminished when 13-cis-retinoic acid was added.
We present in this poster a new in vitro acne model for the discovery or validation of ingredients, based on arachidonic acid stimulation of hiPSC derived sebocytes. This model displays hallmarks of acne development including increased sebum production and proinflammatory cytokine secretion.

An in vitro model of acne hyperseborrhea and inflammation based on hiPSC derived sebocytes