Mok Bo Ram, Shon Su-Ji, Kim A Ram, Simard-Bisson Carolyne, Martel Israël, Germain Lucie, Kim Dong Hyun, Shin Jung U
Department of Biomedical Science, CHA University, Seongnam 13488, Korea.
Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, and Department of Surgery, Faculty of Medicine, Université Laval, CHU de Québec-Université Laval Research Centre, Québec, QC G1J1Z4, Canada.
Pharmaceutics. 2022 Jun 7;14(6):1211. doi: 10.3390/pharmaceutics14061211.
Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases.
最近，已开发出各种类型的体外重建3D皮肤模型用于药物测试和疾病建模。在此，我们对一种自组装重建皮肤等效物（RSE）进行了结构和功能验证，并使用自组装RSE开发了一种IL-17a诱导的体外银屑病样模型。采用组织工程方法构建自组装RSE。使用分泌自身细胞外基质（ECM）的成纤维细胞生成真皮层，并通过将角质形成细胞接种在真皮层上来重建表皮层。为了生成银屑病模型，在气液界面培养期间向培养基中添加IL-17A。自组装RSE形成了完全分化的表皮层、完善的基底膜和真皮胶原沉积。此外，根据经合组织TG439性能标准对自组装RSE进行了20种参考化学品的测试，其总体敏感性、特异性和准确性分别为100%、90%和95%。经IL-17a处理的银屑病RSE模型表现出银屑病表皮特征，如表皮过度增殖、角化不全以及KRT6、KRT17、hBD2和S100A9表达增加。因此，我们的结果表明，一种在结构和功能上模拟人类皮肤的自组装RSE在测试各种药物或化妆品成分以及模拟炎症性皮肤病方面具有巨大潜力。
