摘要：科研人员培育出了一种具有人工肝脏的小鼠模型，它可能有助于优化药物开发。在动物模型中进行的实验药物的前临床测试在一定程度上依赖于科研人员对药物是否能够安全有效地在人体内代谢的预测能力。但是小鼠和人类的药物代谢的差异常常让这类在临床实验中例行地进行的评估变得具有挑战性。为了解决这个挑战，Sangeeta N. Bhatia及其同事使用组织工程技术开发出了有人工肝脏的“拟人”小鼠，这些肝脏是在实验室中用人肝细胞制造的。这组作者让人肝细胞和小鼠皮肤细胞一起生长，并把这些细胞封装在一种含有促进细胞合成和分泌维持生命的分子的能力的肽的聚合物骨架中。这组作者然后把这种“肝脏”移植到了小鼠的皮下或体腔。这组作者报告说，这些肝脏有效地移植了过去，而且这些小鼠在数周时间里展现出了人类肝脏的功能，包括人类蛋白质的合成以及人类药物代谢。这种人工肝脏制造出了功能性人类药物代谢酶，帮助监测了人类代谢物的代谢谱，并且帮助了对药物之间的毒性相互作用的建模。这组作者说，在不到2周的时间里，这种技术可以培育出能够精确地重演人类生理特征的拟人小鼠，而且有可能帮助优化药物开发。
生物探索推荐英文论文摘要：
Humanized mice with ectopic artificial liver tissues
Abstract
“Humanized” mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug–drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of “major” human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.
