Skin Disease Models In Vitro and Inflammatory Mechanisms: Predictability for Drug Development.

Investigative skin biology, analysis of human skin diseases, and numerous clinical and pharmaceutical applications rely on skin models characterized by reproducibility and predictability. Traditionally, such models include animal models, mainly rodents, and cellular models. While animal models are highly useful in many studies, they are being replaced by human cellular models in more and more approaches amid recent technological development due to ethical considerations. The culture of keratinocytes and fibroblasts has been used in cell biology for many years. However, only the development of co-culture and three-dimensional epidermis and full-skin models have fundamentally contributed to our understanding of cell-cell interaction and cell signalling in the skin, keratinocyte adhesion and differentiation, and mechanisms of skin barrier function. The modelling of skin diseases has highlighted properties of the skin important for its integrity and cutaneous development. Examples of monogenic as well as complex diseases including atopic dermatitis and psoriasis have demonstrated the role of skin models to identify pathomechanisms and drug targets. Recent investigations have indicated that 3D skin models are well suitable for drug testing and preclinical studies of topical therapies. The analysis of skin diseases has recognized the importance of inflammatory mechanisms and immune responses and thus other cell types such as dendritic cells and T cells in the skin. Current developments include the production of more complete skin models comprising a range of different cell types. Organ models and even multi-organ systems are being developed for the analysis of higher levels of cellular interaction and drug responses and are among the most recent innovations in skin modelling. They promise improved robustness and flexibility and aim at a body-on-a-chip solution for comprehensive pharmaceutical in vitro studies.