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 after biotransformation, which demonstrates the potentially adverse effects of metabolites on embryotoxicity. The metaEST platform provides a promising tool to increase the predictive power of the current EST assay by more comprehensively including and better reflecting physiological processes in in vitro tests.

Show object

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Microfluidic Multitissue Platform for Advanced Embryotoxicity Testing In Vitro ; volume:6 ; number:13 ; year:2019 ; extent:13 ; Advanced science ; 6, Heft 13 (2019) (gesamt 13)

Contributors, Places and Time

• Creator: Boos, Julia Alicia ; Misun, Patrick M. ; Michlmayr, Astrid ; Hierlemann, Andreas ; Frey, Olivier

Further information

• DOI: 10.1002/advs.201900294
• URN: urn:nbn:de:101:1-2022073111262946118552
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.