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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2018 (publ. 2017, arch)     Display Documents



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ID: 744104.0, MPI für molekulare Biomedizin / Jahrbuch 2018 (publ. 2017, arch)
A scalable approach for the generation of human pluripotent stem cell-derived hepatic organoids with sensitive hepatotoxicity features
Authors:Sgodda, M.; Dai, Z.; Zweigerdt, R.; Sharma, A. D.; Ott, M.; Cantz, T.
Date of Publication (YYYY-MM-DD):2017-07-12
Title of Journal:Stem Cells Dev
Start Page:in press
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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. Here, we report a scalable 3D suspension culture system, in which PSC-derived hepatic cells can be maintained for up to three 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.
External Publication Status:published
Document Type:Article
Communicated by:MPI für molekulare Biomedizin
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Hannover Medical School, Translational Hepatology and Stem Cell Biology ; Dai.Zhen@mh-hannover.de. Hannover Medical School, Leibniz Research Laboratories for Artificial Organs, Hannover, Germany ; zweigerdt.robert@mh-hannover.de. Hannover Medical School ; sharma.amar@mh-hannover.de. Hannover Medical School ; ott.michael@mh-hannover.de. Hannover Medical School, Translational Hepatology and Stem Cell Biology ; cantz.tobias@mh-hannover.de.
Identifiers:ISSN:1557-8534 (Electronic) 1547-3287 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28699415 [ID No:2]
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