In Vitro Tissue Model of Psoriasis
DESCRIPTION (provided by applicant): Psoriasis is a chronic inflammatory and proliferative skin disease that affects 2-3% of the population in Western countries and an estimated 80 million people worldwide. The disease causes disfiguration in 10- 30% of cases and arthiritis in 10-15% of patients. Although attempts are made to model aspects of psoriasis in animals, none of the models reproduce the complex psoriatic phenotypes that are observed in humans. The availability of an in vitro psoriasis model to screen candidate drugs and to gain a better understanding of the biological mechanisms involved in psoriatic disease would be valuable. During Phase I, a human cell based in vitro psoriatic tissue equivalent (PTE) will be developed. Keratinocytes, fibroblasts, dendritic cells, and T-cells will be harvested from psoriatic patient samples and used to reconstruct highly differentiated skin tissues. The histology, ultrastructure, cytokine release, and protein expression of the PTE will be characterized with emphasis on characteristics distinctive of psoriatic tissue. Comparisons to involved and uninvolved skin samples from psoriatic patients will be made. Finally, an overall assessment of the PTE feasibility for commercial purposes will be made. We anticipate that the PTE will have advantages over current animal models due to cost, its human origin, ability to be adapted to high throughput screening formats, and the possibility of modeling different psoriatic phenotypes.
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