A hepatocyte spheroid bioassay system for drug discovery

说明（申请人提供）：肝脏是代谢外源性物质和药物的最重要器官。肝细胞（hepatocytes）常用于检测药物代谢和肝毒性。培养中的肝细胞可以形成球状体，其表现出更高的肝脏特异性功能，并在培养中更长时间地维持高活力。这项研究旨在开发 采用肝细胞球状体用于筛选目的和代谢研究的集成系统。在第一阶段的研究中，我们将开发一个高通量的筛选系统，适合与小型化生物人工肝整合，用于此类研究。我们还将展示肝细胞球体的遗传代谢工程。通过使用固定有最相关的DNA序列的cDNA微阵列将促进结果的分析。拟议的工作将填补高通量筛选的生物测定系统的关键需求。 拟议的商业应用：该项目将开发一个使用肝细胞的综合生物测定系统。 这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.