The Development of Human Ex Vivo Models of Inflammatory Skin Conditions

Abstract

Traditional research in inflammatory dermatoses has relied on animal models and reconstructed human epidermis to study these conditions. However, these models are limited in replicating the complexity of real human skin and reproducing the intricate pathological changes in skin barrier components and lipid profiles. To address this gap, we developed experimental models that mimic various human inflammatory skin phenotypes. Human ex vivo skins were stimulated with various triggers, creating models for inflammation-induced angiogenesis, irritation response, and chronic T-cell activation. We assessed the alterations in skin morphology, cellular infiltrates, cytokine production, and epidermal lipidomic profiles. In the pro-angiogenesis model, we observed increased mast cell degranulation and elevated levels of angiogenic growth factors. Both the irritant and chronic inflammation models exhibited severe epidermal disruption, along with macrophage infiltration, leukocyte exocytosis, and heightened cytokine levels. Lipidomic analysis revealed minor changes in the pro-angiogenesis model, whereas the chronic inflammation and irritant models exhibited significant decreases in barrier essential ceramide subclasses and a shift toward shorter acyl chain lengths (<C18), indicating skin barrier instability. Additionally, the irritant and chronic inflammation models are responsive to immunosuppressants. These models hold promise for advancing scientific understanding and the development of therapeutic and skincare solutions for individuals afflicted by compromised skin conditions.

Screening of the Skin-Regenerative Potential of Antimicrobial Peptides: Clavanin A, Clavanin-MO, and Mastoparan-MO

“…The hOSEC model stands out as an ex vivo system that closely mimics the physiological conditions of human skin. Currently, this alternative model for analyzing the safety and efficacy of various compounds for wound treatment, avoiding the use of animals, is a valuable tool in the validation of compounds for topical and transdermal applications [31]. Ex vivo models that use human skin explants from elective plastic surgery provide a valuable tool to analyze the effect of various molecules in the early stages of the healing process.…”