Journal
STEM CELLS AND DEVELOPMENT
Volume 26, Issue 20, Pages 1490-1504Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2017.0023
Keywords
hepatic PSC derivatives; organoid culture; scalable culture; toxicity assays
Funding
- German Research Foundation (DFG)
- German Research Foundation (Cluster of Excellence REBIRTH DFG) [EXC62/3]
- German Research Foundation (Collaborative Research Center ) [SFB738]
- state of Lower Saxony (R2N consortium)
- German Ministry for Education and Science (BMBF) [13 N12606, 13 N14086]
- StemBANCC (Innovative Medicines Initiative) [115439-2]
- StemBANCC (European Union)
- StemBANCC (EFPIA)
- TECHNOBEAT (European Union H2020) [668724]
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The quest for physiologically active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC)-derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided. In this study, we report a scalable 3D suspension culture system, in which PSC-derived hepatic cells can be maintained for up to 3 weeks with stable gene expression profiles and metabolic features in a suspension culture system ranging from a 1.5 mL up to a 15 mL. Adjustments of culture conditions and, most importantly, the size of the organoids resulted in the robust generation of hepatic organoids consisting of a quite homogenous cell population. Importantly, the generation of these hepatic organoids was highly reproducible and allowed, in contrast to hepatic PSC derivatives in 2D culture conditions, a sensitive assessment of acetaminophen-related toxicity, the most common source for drug-induced liver failure.
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