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Body-on-a-chip: Microfluidic co-culture platform for embryotoxicity testing at the embryo-placental interface
A microfluidic platform for advanced embryotoxicity testing in vitro is established. The 'body-on-a-chip' approach is used to combine an in vitro model of the placental barrier and 3D embryoid bodies (model for early embryonic development) to perform embryotoxicity studies.
Keywords: 3D microtissues, microfluidics, body-on-a-chip, embryotoxicity, embryoid bodies, placental barrier
Assessing the toxicity of drugs in embryonic development still constitutes a major challenge in current cell-based assays. Most in vitro assays only focus on the embryo itself but do not include systemic processes happening in the human body. In a recent study [1], we investigated the influence of liver metabolism on the embryotoxic potential of drugs. We used a dedicated microfluidic hanging-drop platform to co-culture 3D embryoid bodies (EBs) and 3D human primary liver microtissues (hLiMTs). We found a 4-fold lower toxic concentration of the prodrug cyclophosphamide upon metabolic transformation in the liver, as the embryotoxic metabolites caused impaired development.
In a next step, we aim to further improve this platform by including an in vitro model of the placental barrier, which is a pivotal organ for proper embryonic development.
[1] Boos J.A. et al. Microfluidic Multitissue Platform for Advanced Embryotoxicity Testing In Vitro. Advanced Science. 2019.
Assessing the toxicity of drugs in embryonic development still constitutes a major challenge in current cell-based assays. Most in vitro assays only focus on the embryo itself but do not include systemic processes happening in the human body. In a recent study [1], we investigated the influence of liver metabolism on the embryotoxic potential of drugs. We used a dedicated microfluidic hanging-drop platform to co-culture 3D embryoid bodies (EBs) and 3D human primary liver microtissues (hLiMTs). We found a 4-fold lower toxic concentration of the prodrug cyclophosphamide upon metabolic transformation in the liver, as the embryotoxic metabolites caused impaired development. In a next step, we aim to further improve this platform by including an in vitro model of the placental barrier, which is a pivotal organ for proper embryonic development.
[1] Boos J.A. et al. Microfluidic Multitissue Platform for Advanced Embryotoxicity Testing In Vitro. Advanced Science. 2019.
In this project you will learn
• Mammalian cell culture
• 3D microtissue culturing
• Microfabrication (microfluidic chip fabrication)
• Designing and optimizing microfluidic chips
• Biochemical assays and staining methods
In this project you will learn • Mammalian cell culture • 3D microtissue culturing • Microfabrication (microfluidic chip fabrication) • Designing and optimizing microfluidic chips • Biochemical assays and staining methods