Long-Term and Clinically Relevant Full-Thickness Human Skin Equivalent for Psoriasis
ACS Applied Bio Materials, vol. 3, pp. 6639–6647
Abstract
High Resolution Image Download MS PowerPoint Slide Psoriasis is an incurable, immune-mediated inflammatory disease characterized by the hyperproliferation and abnormal differentiation of keratinocytes. To study in depth the pathogenesis of this disease and possible therapy options suitable, pre-clinical models are required. Three-dimensional skin equivalents are a potential alternative to simplistic monolayer cultures and immunologically different animal models. However, current skin equivalents lack long-term stability, which jeopardizes the possibility to simulate the complex disease-specific phenotype followed by long-term therapeutic treatment. To overcome this limitation, the cell coating technique was used to fabricate full-thickness human skin equivalents (HSEs). This rapid and scaffold-free fabrication method relies on coating cell membranes with nanofilms using layer-by-layer assembly, thereby allowing extended cultivation of HSEs up to 49 days. The advantage in time is exploited to develop a model that not only forms a disease phenotype but can also be used to monitor the effects of topical or systemic treatment. To generate a psoriatic phenotype, the HSEs were stimulated with recombinant human interleukin 17A (rhIL-17A). This was followed by systemic treatment of the HSEs with the anti-IL-17A antibody secukinumab in the presence of rhIL-17A. Microarray and RT-PCR analysis demonstrated that HSEs treated with rhIL-17A showed downregulation of differentiation markers and upregulation of chemokines and cytokines, while treatment with anti-IL-17A antibody reverted these gene regulations. Gene ontology analysis revealed the proinflammatory and chemotactic effects of rhIL-17A on the established HSEs. These data demonstrated, at the molecular level, the effects of anti-IL-17A antibody on rhIL-17A-induced gene regulations. This shows the physiological relevance of the developed HSE and opens venues for its use as an alternative to ex vivo skin explants and animal testing.
Authors 8
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DWI – Leibniz Institute for Interactive Materials
Affiliation as printed
DWI-Leibniz Institute for Interactive Materials, Forkenbeckstrasse 50, Aachen 52074, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Dermatology and Allergology, University Hospital, RWTH Aachen University, Aachen 52074, Germany
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DWI – Leibniz Institute for Interactive Materials
Affiliation as printed
DWI-Leibniz Institute for Interactive Materials, Forkenbeckstrasse 50, Aachen 52074, Germany
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National Institute for Materials Science · DWI – Leibniz Institute for Interactive Materials
Affiliation as printed
DWI-Leibniz Institute for Interactive Materials, Forkenbeckstrasse 50, Aachen 52074, Germany
Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Dermatology and Allergology, University Hospital, RWTH Aachen University, Aachen 52074, Germany
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Affiliation as printed
Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan
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A. N. Nesmeyanov Institute of Organoelement Compounds · DWI – Leibniz Institute for Interactive Materials
Affiliation as printed
A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Science, Vavilova 28, Moscow 119991, Russia
DWI-Leibniz Institute for Interactive Materials, Forkenbeckstrasse 50, Aachen 52074, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Dermatology and Allergology, University Hospital, RWTH Aachen University, Aachen 52074, Germany
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