540 A Novel Ex Vivo Assay Platform to Pre-Clinically Evaluate Candidate Hypo- or Hyperpigmentation-Inducing Agents in Human Epidermis

In vitro models to investigate pigmentation disorders inadequately capture the complex neuroectodermal-mesodermal signaling interplay controlling human epidermal melanogenesis. Here, we aimed at assessing suitability of a standardized ex vivo skin organ culture as rapid detection-system qualitatively and quantitatively assess effects topically or systemically applied candidate modulators, under clinically relevant conditions. Full-thickness samples were cultured in serum-free supplemented medium exposed selected test agents (hyperpigmentation controls: [Nle4, DPhe7]-α-melanocyte-stimulating hormone (α-MSH) forskolin; hypopigmentation control: kojic acid 4-butylresorcinol) for 3 days vivo, either through systemic topical delivery routes, followed by changes tyrosinase activity situ, gp100 protein expression (immunofluorescence microscopy) melanin content (Warthin-Starry histochemistry) epidermis. We show that administration (i.e. culturing medium) α-MSH forskolin significantly stimulates production. Moreover, demonstrate application DMSO enhances expression, production vivo. Addition inhibitors, 4-butylresorcinol, prevents melanogenesis induced treatment. Finally, utilized this preclinical model identify novel, applicable, drug-free hyperpigmentation active promoter “UV-free tanning”. conclusion, introduce pragmatic short-term assay, which provides simple, accessible, sensitive, quantifiable, relevant, pre-clinical platform identification modulators manage hyper- disorders.