Reconstructed Human Oral Tissues

描述(申请人提供)：第一阶段研究采用了原代培养方法，以获得可靠的正常人类口腔上皮(NHBE)细胞来源。组织培养方法被发展为诱导NHBE细胞分化为三维器官型组织。鉴定表明，该组织复制了许多天然口腔组织的组织学、蛋白质表达和屏障功能特性。最初的实验调查了使用NHBE组织来预测口腔刺激性和经口给药速率。最后，对纸巾生产成本的经济评估表明，NHBE产品似乎在商业上是可行的。 第二阶段工作计划将在第一阶段结果的基础上进一步发展NHBE和其他相关的、更复杂的口腔粘膜模型。将优化NHBE培养条件，并确定产生牙龈表型和结合固有层的条件。将确定预测口腔刺激性的方案，并将以更全面的方式研究组织用于口腔给药的用途。最后，将进行针对基本口腔生物学现象的研究，即抗菌肽调节和艾滋病毒感染。

DESCRIPTION (provided by applicant): Phase I research adapted primary culture methods to obtain a reliable source of normal human buccal epithelial (NHBE) cells. Tissue culture methods were developed to induce the NHBE cells to differentiate into a three-dimensional organotypic tissue. Characterization showed that the tissue reproduced many of the histological, protein expression, and barrier function properties of native buccal tissue. Initial experiments investigated use of the NHBE tissue for predicting oral irritation and transbuccal drug delivery rates. Finally, an economic evaluation of costs involved in tissue production showed that an NHBE product appears to be commercially feasible. The Phase II work plan will expand upon the results of Phase I to further develop the NHBE and other related, and more complex, oral mucosal models. NHBE culture conditions will be optimized and conditions to produce a gingival phenotype and incorporate lamina propria will be determined. Protocols to predict oral irritation will be determined and use of the tissue for transbuccal drug delivery will be studied in a more comprehensive manner. Finally, studies addressing basic oral biology phenomena, namely anti-microbial peptide regulation and HIV infection, will be performed.