Student Seoul National University Seoul National University, Seoul-t'ukpyolsi, Republic of Korea
Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by epidermal barrier dysfunction, immune dysregulation, and microbial dysbiosis. Current in vitro and animal models fail to replicate the human-specific pathophysiology of AD, particularly the interactions between immune cells, skin, and vascular components, limiting therapeutic advancements. To address this, we developed vascularized skin assembloids derived from human-induced pluripotent stem cells (hiPSCs), providing a physiologically relevant platform for AD research.
This model integrates hiPSC-derived multilayered skin organoids with vascular organoids to replicate the structural and functional complexity of human skin. Incorporating immune cells, including T cells, macrophages, and dendritic cells, it enables precise modeling of immune-vascular interactions. Upon exposure to environmental triggers, such as allergens (e.g., house dust mites) or microbial antigens (e.g., bacterial metabolites), the assembloids faithfully recapitulate hallmark AD phenotypes, including epidermal barrier disruption, elevated Th2 cytokines (IL-4, IL-13), immune cell infiltration, and inflammatory tissue remodeling, closely resembling clinical AD pathology.
Histological and molecular analyses revealed bacterial colonization, chronic inflammation, and heightened immune activation, effectively replicating the persistent nature of AD. Therapeutic evaluation demonstrated that Dupilumab and JAK inhibitors significantly reduced Th2-driven inflammation, restored epidermal barrier integrity, and normalized immune responses, validating the platform’s translational potential.
Beyond AD, this versatile platform holds promise for studying other inflammatory skin diseases and supporting high-throughput drug discovery. By replicating key AD phenotypes and immune-vascular interactions within a human-specific microenvironment, these vascularized skin assembloids establish a new benchmark for preclinical research and accelerate the development of precision therapies.
Funding Source: This work was supported by the Korean Fund for Regenerative Medicine (KFRM) grant (the Ministry of Science and ICT, the Ministry of Health & Welfare) No. 23A0101L1 (2710001356, 00215812) funded by the Korea government.
