Skin Models with Physiopathological Relevance for Pre-Clinical Testing

• Grant number: 23/12236-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2025
• End date: October 31, 2030
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Silvya Stuchi Maria-Engler
• Grantee: Silvya Stuchi Maria-Engler
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Priscila Keiko Matsumoto Martin ; Raquel Leão Orfali ; Renata Fonseca Vianna Lopez ; Ricardo Weinlich ; Valeria Aoki

Abstract

Biological research of the skin, the study of human skin diseases, and various clinical and pharmaceutical applications rely on skin models known for their reproducibility and predictability. Traditionally, these models have included animals, primarily rodents, and cell cultures. However, due to ethical considerations and recent technological advancements, human cell models are gradually replacing animal models. In this context, the co-culture of keratinocytes and fibroblasts, as well as the development of three-dimensional skin models, have represented significant advances in our understanding of cell interaction and signaling in the skin, as well as the mechanisms governing skin barrier function. In vitro models of skin diseases have revealed essential skin characteristics, contributing to our understanding of dermal-epidermal interaction, cell-cell and cell-matrix interactions, responses of dermal and epithelial cells to biological signals and pharmacological agents, and the effects of drugs and growth factors on skin reconstruction processes. Therefore, the development of genetically controlled and well-characterized skin models has significant implications not only for scientists and physicians but also for manufacturers, consumers, regulatory bodies, and animal welfare organizations. As the cells composing human skin tissue develop within an organized three-dimensional (3D) matrix and are surrounded by neighboring cells, monolayer cell cultures (2D) cannot adequately reproduce the physiological architecture of the skin. Various types of recombinant human skin, also known as artificial skin, that provide this crucial 3D structure have already been reconstructed in vitro. In this second thematic project, our research group aims to enhance the existing reconstructed skin model with a focus on reproducing diseases in vitro through innovative methodological approaches. We believe this will allow us to establish a more robust platform for discovering new dermatological drugs, expanding our understanding of the pathophysiology of both tumor and non-tumor skin conditions. We plan to direct our efforts towards the following subprojects, using meticulously reconstructed in vitro three-dimensional human skin models to mimic various skin diseases, including Atopic Dermatitis, Epidermolysis Bullosa, Depigmenting Diseases, Melanoma Resistant to Targeted Oncogene Inhibitors, and Age-Related Melanoma. Our work is characterized by a deep understanding of fundamental mechanisms, combining multidisciplinary approaches and a wide range of technologies, while also establishing clinical collaborations. Recently, our team initiated projects aimed at studying the molecular mechanisms involved in melanoma, emphasizing the presence of intratumoral heterogeneity in a subset of melanomas and identifying a prognostic signature. (AU)