In Vitro Tissue Model of Psoriasis

描述（由申请人提供）：牛皮癣是一种慢性炎症性和增殖性皮肤病，影响西方国家2-3%的人口，全球估计有8000万人。该病导致10-30%的病例毁容，10-15%的患者患关节炎。尽管人们试图在动物身上建立牛皮癣的模型，但没有一个模型能再现在人类身上观察到的复杂的牛皮癣表型。利用体外银屑病模型筛选候选药物并更好地了解银屑病的生物学机制将是有价值的。在第一阶段，将开发基于体外银屑病组织当量（PTE）的人类细胞。角质形成细胞、成纤维细胞、树突状细胞和t细胞将从银屑病患者样本中收集，用于重建高度分化的皮肤组织。我们将对PTE的组织学、超微结构、细胞因子释放和蛋白表达进行描述，重点介绍银屑病组织的特征。将对银屑病患者的受累和未受累皮肤样本进行比较。最后，将对PTE用于商业目的的可行性进行全面评估。我们预计，由于成本、人类起源、适应高通量筛选格式的能力以及建模不同银屑病表型的可能性，PTE将比目前的动物模型具有优势。

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.