Li Albert P
Advanced Pharmaceutical Sciences Inc., Columbia, Maryland 21045, USA.
ALTEX. 2008;25(1):43-9. doi: 10.14573/altex.2008.1.43.
In vitro human-based experimental systems represent a relevant preclinical tool for the definition of human xenobiotic properties as human-specific xenobiotic properties, by definition, cannot be detected with nonhuman laboratory animals. For the evaluation of human-specific xenobiotic toxicity, the experimental system should have human xenobiotic metabolism as well as cell populations representing the target cells in vivo. Based on these requirements, we have developed a novel cell culture technology, the Integrated Discrete Multiple Organ Co-culture (IdMOC) system, as an alternative experimental model for the evaluation of xenobiotic toxicity. The IdMOC system employs a wells-in-a-well concept for the co-culturing of cells from different organs as physically separated (discrete) entities in the inner wells, but interconnected by an overlying medium (integrated) in the outer well. The IdMOC system models a multi-organ animal/human in vivo with organs that are physically separated but interconnected by the systemic circulation. The IdMOC allows multi-organ interactions that are absent in the conventional single-cell type cultures. Applications of IdMOC include the evaluation of multiple organ metabolism as well as organ-specific drug distribution and toxicity. A particularly interesting application of IdMOC is the co-culturing of cancer cells and cells representing major organs for the selection of anticancer agents with minimal organ toxicity.
基于人体的体外实验系统是一种相关的临床前工具，用于定义人体异生素特性，因为根据定义，人体特异性异生素特性无法用非人类实验动物检测到。为了评估人体特异性异生素毒性，实验系统应具备人体异生素代谢以及代表体内靶细胞的细胞群体。基于这些要求，我们开发了一种新型细胞培养技术，即整合离散多器官共培养（IdMOC）系统，作为评估异生素毒性的替代实验模型。IdMOC系统采用孔中孔概念，将来自不同器官的细胞作为物理上分离（离散）的实体在内部孔中进行共培养，但通过外部孔中的上层培养基（整合）相互连接。IdMOC系统模拟了一个多器官动物/人体，其器官在物理上是分离的，但通过体循环相互连接。IdMOC允许进行传统单细胞类型培养中不存在的多器官相互作用。IdMOC的应用包括评估多器官代谢以及器官特异性药物分布和毒性。IdMOC一个特别有趣的应用是将癌细胞与代表主要器官的细胞进行共培养，以选择器官毒性最小的抗癌药物。
