Project 5: Skin Equivalents

As the largest organ of the body, the skin is permanently exposed to environmental hazards, radiation, chemical substances and biological agents, thereby forming the first line of immunological defense in the body. However, these factors can lead to serious skin reactions such as skin irritation, inflammation, allergies or cancer. Hence, there is a substantial need to screen and assess the toxicity of agents and the identification of efficacious novel drug candidates for the skin.

We are currently developing a novel human 3D immune competent full-thickness skin model according to the 3R principles (“replace”, “reduce” and “refine”), for pharmacological and toxicological compound assessment. For this, langerhans cell surrogates are integrated as central initiators of the immune reaction in the skin, implementing skin sensitization and inflammation in the 3D model. To assess the tested compounds, inflammatory pathways are investigated via sequencing and transcriptomic analysis and threshold values will be determined for putative compound classifications and perspectively for high throughput screenings.

Further research includes the integration of additional cell types e.g. melanocytes, melanoma cells or vascularization, allowing distinct disease modelling for drug discovery.

Selected publications:

1. Hölken JM, Wurz A-L, Friedrich K, et al. Incorporating immune cell surrogates into a full-thickness tissue equivalent of human skin to characterize dendritic cell activation. Scientific Reports. 2024/12/04 2024;14(1):30158. doi:10.1038/s41598-024-81014-9
2. Holken JM, Friedrich K, Merkel M, et al. A human 3D immune competent full-thickness skin model mimicking dermal dendritic cell activation. Front Immunol. 2023;14:1276151. doi:10.3389/fimmu.2023.1276151
3. Holken JM, Teusch N. The Monocytic Cell Line THP-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells. Int J Mol Sci. Jan 11 2023;24(2)doi:10.3390/ijms24021452