The development of a 3D immunocompetent model of human skin
The development of a 3D immunocompetent model of human skin
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DOI：
10.1088/1758-5082/5/3/035011
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发表时间：
2013-09-01
期刊：
影响因子：
9
通讯作者：
Ghaemmaghami, Amir M.
中科院分区：
文献类型：
--
作者：
Chau, David Y. S.;Johnson, Claire;Ghaemmaghami, Amir M.
作为第一道防线，皮肤经常暴露于各种生物、物理和化学伤害。因此，从安全性评估和监管的角度来看，确定新化学品的皮肤致敏潜力至关重要。考虑到动物模型与人类的生物学相关性值得怀疑，以及限制或停止使用动物模型进行安全性测试的伦理和监管压力，需要开发简单但生理学相关的人类皮肤模型。在此，我们描述了一种新的免疫活性的3D人体皮肤模型的构建，包括与角质形成细胞和成纤维细胞共培养的树突状细胞。该模型培养系统易于与容易获得的组分组装，并且重要的是，可以分离成其组成性个体层，以允许进一步深入了解细胞-细胞相互作用和皮肤致敏机制的详细研究。在这项研究中，使用不可降解的微纤维支架和载有细胞的凝胶，我们设计了一个多层3D免疫活性模型，由角质形成细胞和成纤维细胞组成，其中散布着树突状细胞。我们已经使用共聚焦显微镜，免疫组织化学和扫描电子显微镜的组合，其特征在于该模型，并已显示分化的表皮层和形成的表皮屏障。至关重要的是，模型中的免疫细胞能够迁移，并对皮肤致敏剂的刺激保持反应，即使在低浓度下也是如此。因此，我们建议这种新的生物学相关的皮肤模型将被证明是有价值的，在研究过敏性接触性皮炎和其他皮肤病理学的机制在人类。一旦完全优化，该模型还可用作测试新化学品和药物先导物的致敏潜力的平台。
As the first line of defence, skin is regularly exposed to a variety of biological, physical and chemical insults. Therefore, determining the skin sensitization potential of new chemicals is of paramount importance from the safety assessment and regulatory point of view. Given the questionable biological relevance of animal models to human as well as ethical and regulatory pressure to limit or stop the use of animal models for safety testing, there is a need for developing simple yet physiologically relevant models of human skin. Herein, we describe the construction of a novel immunocompetent 3D human skin model comprising of dendritic cells co-cultured with keratinocytes and fibroblasts. This model culture system is simple to assemble with readily-available components and importantly, can be separated into its constitutive individual layers to allow further insight into cell-cell interactions and detailed studies of the mechanisms of skin sensitization. In this study, using non-degradable microfibre scaffolds and a cell-laden gel, we have engineered a multilayer 3D immunocompetent model comprised of keratinocytes and fibroblasts that are interspersed with dendritic cells. We have characterized this model using a combination of confocal microscopy, immuno-histochemistry and scanning electron microscopy and have shown differentiation of the epidermal layer and formation of an epidermal barrier. Crucially the immune cells in the model are able to migrate and remain responsive to stimulation with skin sensitizers even at low concentrations. We therefore suggest this new biologically relevant skin model will prove valuable in investigating the mechanisms of allergic contact dermatitis and other skin pathologies in human. Once fully optimized, this model can also be used as a platform for testing the allergenic potential of new chemicals and drug leads.