Ex Vivo Culture Models of Hidradenitis Suppurativa for Defining Molecular Pathogenesis and Treatment Efficacy of Novel Drugs

Abstract Hidradenitis suppurativa (HS) is a complex inflammatory and debilitating skin disease for which no effective treatment is available currently. This is partly because of the lack of adequate human or animal models to define the pathobiology of the disease. Here, we describe the development of air-liquid (A-L) interface, liquid-submersion (L-S) and bioreactor (Bio) ex vivo skin culture models. All three ex vivo platforms were effective for culturing skin samples up to 14 days. Tissue architecture and integrity remained intact for at least 3 days for healthy skin and 14 days for HS skin. Up to day-3, no significant differences were observed in % early apoptotic cells among all three platforms. However, an increase was observed in late apoptotic/necrotic cells in HS skin at day-3 in A-L and Bio culture. These cultures efficiently support the growth of various cells populations, including keratinocytes and immune cells. Profiling inflammatory gene signatures in HS skin from these ex vivo cultures showed dynamic expression changes at day-3 and day-14. All three culture platforms are necessary to represent the inflammatory gene status of HS skin at day-0, suggesting that not all gene clusters are identically altered in each culture method. Similarly, cytokine/chemokine profiling of the supernatants from vehicle- and drug-treated ex vivo HS cultures again showed better prediction of drug efficacy against HS. Overall, development of these three culture systems collectively provides a powerful tool to uncover the pathobiology of HS progression and screen various drugs against HS.