Title |
Multi-cell type human liver microtissues for hepatotoxicity testing
|
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Published in |
Archives of Toxicology, November 2012
|
DOI | 10.1007/s00204-012-0968-2 |
Pubmed ID | |
Authors |
S. Messner, I. Agarkova, W. Moritz, J. M. Kelm |
Abstract |
Current 2-dimensional hepatic model systems often fail to predict chemically induced hepatotoxicity due to the loss of a hepatocyte-specific phenotype in culture. For more predictive in vitro models, hepatocytes have to be maintained in a 3-dimensional environment that allows for polarization and cell-cell contacts. Preferably, the model will reflect an in vivo-like multi-cell type environment necessary for liver-like responses. Here, we report the characterization of a multi-cell type microtissue model, generated from primary human hepatocytes and liver-derived non-parenchymal cells. Liver microtissues were stable and functional for 5 weeks in culture enabling, for example, long-term toxicity testing of acetaminophen and diclofenac. In addition, Kupffer cells were responsive to inflammatory stimuli such as LPS demonstrating the possibility to detect inflammation-mediated toxicity as exemplified by the drug trovafloxacin. Herewith, we present a novel 3D liver model for routine testing in 96-well format capable of reducing the risk of unwanted toxic effects in the clinic. |
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Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 51 | 17% |
Student > Master | 50 | 16% |
Student > Bachelor | 27 | 9% |
Other | 22 | 7% |
Other | 32 | 10% |
Unknown | 58 | 19% |
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Engineering | 25 | 8% |
Medicine and Dentistry | 19 | 6% |
Other | 31 | 10% |
Unknown | 66 | 21% |