Hepatic organoids for microfluidic drug screening. 2014

Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St., Toronto, ON M5S 3G9, Canada. aaron.wheeler@utoronto.ca.

We introduce the microfluidic organoids for drug screening (MODS) platform, a digital microfluidic system that is capable of generating arrays of individually addressable, free-floating, three-dimensional hydrogel-based microtissues (or 'organoids'). Here, we focused on liver organoids, driven by the need for early-stage screening methods for hepatotoxicity that enable a "fail early, fail cheaply" strategy in drug discovery. We demonstrate that arrays of hepatic organoids can be formed from co-cultures of HepG2 and NIH-3T3 cells embedded in hydrogel matrices. The organoids exhibit fibroblast-dependent contractile behaviour, and their albumin secretion profiles and cytochrome P450 3A4 activities are better mimics of in vivo liver tissue than comparable two-dimensional cell culture systems. As proof of principle for screening, MODS was used to generate and analyze the effects of a dilution series of acetaminophen on apoptosis and necrosis. With further development, we propose that the MODS platform may be a cost-effective tool in a "fail early, fail cheaply" paradigm of drug development.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D004364 Pharmaceutical Preparations Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D046210 Microfluidic Analytical Techniques Methods utilizing the principles of MICROFLUIDICS for sample handling, reagent mixing, and separation and detection of specific components in fluids. Microfluidic Analysis,Analyses, Microfluidic,Analysis, Microfluidic,Analytical Technique, Microfluidic,Analytical Techniques, Microfluidic,Microfluidic Analyses,Microfluidic Analytical Technique,Technique, Microfluidic Analytical,Techniques, Microfluidic Analytical
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056945 Hep G2 Cells A human liver tumor cell line used to study a variety of liver-specific metabolic functions. Cell Line, Hep G2,Cell Line, Hepatoblastoma G2,Hep G2 Cell Line,HepG2 Cells,Hepatoblastoma G2 Cell Line,Cell, Hep G2,Cell, HepG2,Cells, Hep G2,Cells, HepG2,Hep G2 Cell,HepG2 Cell
D041681 NIH 3T3 Cells A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/) 3T3 Cells, NIH,NIH-3T3 Cells,3T3 Cell, NIH,Cell, NIH 3T3,Cell, NIH-3T3,Cells, NIH 3T3,Cells, NIH-3T3,NIH 3T3 Cell,NIH-3T3 Cell

Related Publications

Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
October 2020, Nature communications,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
August 2023, Hepatobiliary surgery and nutrition,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
February 2018, Genes,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
January 2024, Methods in molecular biology (Clifton, N.J.),
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
January 2023, Biosensors & bioelectronics,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
May 2016, Bioanalysis,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
May 2022, Acta histochemica,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
October 2020, Nature protocols,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
July 2022, Cell stem cell,
Sam H Au, and M Dean Chamberlain, and Shruthi Mahesh, and Michael V Sefton, and Aaron R Wheeler
August 2022, ACS applied bio materials,
Copied contents to your clipboard!