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Stem Cells Dev. 2017 Oct 15;26(20):1490-1504. doi: 10.1089/scd.2017.0023. Epub 2017 Aug 24.

A Scalable Approach for the Generation of Human Pluripotent Stem Cell-Derived Hepatic Organoids with Sensitive Hepatotoxicity Features.

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1 Research Group Translational Hepatology and Stem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School , Hannover, Germany .
2 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School , Hannover, Germany .
3 Junior Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School , Hannover, Germany .
4 Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School , Hannover, Germany .
5 Twincore Centre for Experimental and Clinical Infection Research , Hannover, Germany .
6 Max Planck Institute for Molecular Biomedicine , Cell and Developmental Biology, Münster, Germany .


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.


hepatic PSC derivatives; organoid culture; scalable culture; toxicity assays

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