Multicellular Skin Organoids as a Unique Modeling Platform for Skin Physiology, Injury, and Disease

This study presents a novel multicellular skin organoid (SO) system that effectively models human skin's complexity, including its microanatomy, functionality, and pathological responses. By culturing a mixture of six key skin cell types for 21 days, the SOs maintained a skin-like layered microstructure and demonstrated functions such as epidermal barrier integrity and melanogenesis. The system was tested for skin physiology using retinol metabolism and barrier integrity with 4kDa Dextran-FITC diffusion. It successfully modeled skin injury through chemical and UVB exposure, showing reactions consistent with known irritation indices and stress responses. Additionally, melanoma cells within the SOs mimicked cancer spread and invasion, providing a reliable platform for studying skin physiology, damage, and cancer in dermatopathology.