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Metabolically Competent Stem Cell Systems: Novel Means to Implement 3Rs in Better Drug Safety Assessment

具有代谢能力的干细胞系统：在更好的药物安全性评估中实施 3R 的新方法

基本信息

批准号：
G0700611/1
负责人：
Roland Wolf
金额：
$ 41.23万
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=G0700611%2F1
关键词：
Metabolically Competent Stem Cell Systems

项目摘要

Bringing novel drugs onto the market is a process that takes 10-15 years and consummates # 400,000,000. More than 10000 compounds enter the preclinical drug discovery and development pipeline of large pharmaceutical companies per annum. The task of these preclinical stages, which rely heavily on animal experimentation, is to predict desired and adverse effects in man. This importantly before investigational new drugs are given to humans in the clinical stages. Thus the life of many animals and of humans is decided in these pre-clinical stages. Animal-derived in vitro tests have been developed to meet commercial pressures and to implement the 3Rs. One of these tests, termed mouse embryonal stem cell toxicity test (mEST) is able to identify compounds that lead to fetal malformations and other toxicities. However, the mEST is only moderately reliable, thus hampering its acceptance by industry and simultaneously the implementation of the 3Rs. Here we will enhance the predictive power of this platform by its ?humanisation?. This will be achieved by employing human umbilical cord stems cells (not human embryonal stem cells) and at the same time by introducing human drug metabolism into these systems. It is anticipated that these novel platforms will reduce the number of animal experimentation, while at the same time improving drug safety.

将新药推向市场是一个需要10-15年的过程，完成了4亿美元。每年有超过10000种化合物进入大型制药公司的临床前药物发现和开发管道。这些临床前阶段的任务主要依赖于动物实验，即在临床阶段将研究性新药用于人类之前，预测对人体的预期作用和不良反应。因此，许多动物和人类的生命就在这些临床前阶段决定。已经开发了动物源性体外试验，以满足商业压力并实施3R。这些测试之一，称为小鼠胚胎干细胞毒性测试（mEST）能够识别导致胎儿畸形和其他毒性的化合物。然而，mEST的可靠性不高，因此阻碍了工业界对其的接受，同时也阻碍了3R的实施。在这里，我们将提高预测能力，这个平台的？人性化？这将通过使用人脐带干细胞（而不是人胚胎干细胞）并同时通过将人药物代谢引入这些系统来实现。预计这些新平台将减少动物实验的数量，同时提高药物安全性。