Microfluidic Multitissue Platform for Advanced Embryotoxicity Testing In Vitro.

ABSTRACT: The integration of metabolic competence in developmental toxicity assays in vitro is of fundamental importance to better predict adverse drug effects. Here, a microfluidic hanging-drop platform is presented that seamlessly integrates liver metabolism into the embryonic stem cell test (EST). Primary human liver microtissues (hLiMTs) and embryoid bodies (EBs) are combined in the same fluidic network, so that hLiMT-generated metabolites are directly transported to the EBs. Gravity-driven flow through the network enables continuous intertissue communication, constant medium turnover, and, most importantly, immediate exchange of metabolites. As a proof of concept, the prodrug cyclophosphamide is investigated and a fourfold lower ID50 concentration (50% inhibition of EB differentiation) is found

SUBMITTER: Boos JA 

PROVIDER: S-EPMC6662399 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature