Kettenhofen Ralf, Bohlen Heribert
Axiogenesis AG, Nattermann Allee 1, 50829 Cologne, Germany.
Drug Discov Today. 2008 Aug;13(15-16):702-7. doi: 10.1016/j.drudis.2008.06.011. Epub 2008 Jul 24.
The exact prediction of the clinical behavior of drugs represents one of the most difficult duties in preclinical drug development. The use of cell-based assay systems underpins the development of many drug candidates, but owing to the artificial character of many of these systems, cell response and physiological behavior seem to be mutually exclusive. Embryonic stem cell-derived cells represent a system that may address the disconnect between the behavior of cultured cells and cells in situ. While undifferentiated ES cells allow standardization, expansion and genetic manipulation, the differentiated cells provide a reflection of the normal physiological image of their primary counterpart. We compare common models to detect cardiac toxicity with an assay system comprising in vitro differentiated pure cardiomyocytes.
准确预测药物的临床行为是临床前药物研发中最具挑战性的任务之一。基于细胞的检测系统是许多候选药物研发的基础，但由于这些系统大多具有人为特性，细胞反应和生理行为似乎相互排斥。胚胎干细胞衍生细胞代表了一种可能解决培养细胞与原位细胞行为脱节问题的系统。未分化的胚胎干细胞可实现标准化、扩增和基因操作，而分化细胞则反映了其原始对应细胞的正常生理状态。我们将用于检测心脏毒性的常见模型与包含体外分化的纯心肌细胞的检测系统进行了比较。
