Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction

International Journal of Molecular Sciences
Pujan K DesaiGlauco R Souza

Abstract

There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces. With this platform, spheroids can be rapidly assembled and easily handled, while replicating native liver function. We assembled spheroids of primary human hepatocytes in a 384-well format and maintained this culture over five days, including a 72 h induction period with known CYP450 inducers/inhibitors. CYP450 activity and viability in the spheroids were assessed and compared in parallel with monolayers. CYP450 activity was induced/inhibited in spheroids as expected, separate from any toxic response. Spheroids sh...Continue Reading

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Citations

Jan 23, 2019·Journal of Tissue Engineering and Regenerative Medicine·Joao N FerreiraGlauco R Souza
May 19, 2020·Critical Reviews in Toxicology·Xihui ZhangLeshuai W Zhang
Mar 28, 2019·Journal of Cell Communication and Signaling·Priyanka RayMohiuddin Quadir
Feb 3, 2021·Micromachines·Leslie DonoghuePalaniappan Sethu
Jun 14, 2021·European Biophysics Journal : EBJ·Ilaria TortorellaFrancesco Morena
Oct 7, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Manisha NautiyalMerrie Mosedale
Mar 11, 2019·ACS Biomaterials Science & Engineering·Priyanka RayMohiuddin Quadir
Sep 29, 2021·Molecular Pharmaceutics·Fengjiao LiZhonghua Liu
Oct 7, 2021·ACS Biomaterials Science & Engineering·Elizaveta V KoudanGleb B Sukhorukov

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