A hepatocyte spheroid bioassay system for drug discovery

描述(申请人提供)：肝脏是代谢外源物质和药物的最重要器官。肝细胞是检测药物代谢和肝毒性的常用细胞。培养中的肝细胞可以形成球体，表现出较高的肝脏特异性功能，并在培养中保持较高的存活率。这项拟议的研究是为了发展 一种使用肝细胞球体进行筛查和代谢研究的综合系统。在第一阶段的研究中，我们会发展一套适合与小型生物人工肝整合的高通量筛选系统，以进行这类研究。我们还将演示肝细胞球体的基因代谢工程。结果的分析将通过使用固定了最相关DNA序列的cDNA微阵列来促进。这项拟议的工作将满足高通量筛选对生物检测系统的迫切需求。 建议的商业应用：该项目将开发一个使用肝细胞的综合生物检测系统。它将极大地促进高通量筛选。

Description (provided by applicant): The liver is the most important organ in metabolizing xenobiotics and drugs. Liver cells (hepatocytes) are used frequently in testing drug metabolism and hepatotoxicity. Hepatocytes in culture can form spheroids that exhibit higher liver-specific functions and sustain high viability longer in culture. This proposed research is to develop an integrated system employing hepatocyte spheroids for both screening purposes and for metabolic studies. In phase I studies, we will develop a high throughput screening system suitable for integration with a miniaturized bioartificial liver for such studies. We will also demonstrate genetic metabolic engineering of hepatocyte spheroids. The analysis of the results will be facilitated by the use of a cDNA microarray immobilized with most relevant DNA sequences. The proposed work will fill a critical need for bioassay systems for high throughput screening. PROPOSED COMMERCIAL APPLICATION: This project will develop an integrated bioassay system using hepatocytes. It will greatly facilitate high throughput screening.