In vitro models for liver toxicity testing
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Griffith_In vitro.pdf
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Author(s)
Soldatow, Valerie Y.
LeCluyse, Edward L.
Griffith, Linda G.
Rusyn, Ivan
Date Issued
2013
Journal
Toxicology Research
Publisher
Royal Society of Chemistry
Citation
Soldatow, Valerie Y., Edward L. LeCluyse, Linda G. Griffith, and Ivan Rusyn. “In Vitro Models for Liver Toxicity Testing.” Toxicol. Res. 2, no. 1 (2013): 23.
Version
Author's final manuscript
Abstract
Over the years, various liver-derived in vitro model systems have been developed to enable investigation of the potential adverse effects of chemicals and drugs. Liver tissue slices, isolated microsomes, perfused liver, immortalized cell lines, and primary hepatocytes have been used extensively. Immortalized cell lines and primary isolated liver cells are currently the most widely used in vitro models for liver toxicity testing. Limited throughput, loss of viability, and decreases in liver-specific functionality and gene expression are common shortcomings of these models. Recent developments in the field of in vitro hepatotoxicity include three-dimensional tissue constructs and bioartificial livers, co-cultures of various cell types with hepatocytes, and differentiation of stem cells into hepatic lineage-like cells. In an attempt to provide a more physiological environment for cultured liver cells, some of the novel cell culture systems incorporate fluid flow, micro-circulation, and other forms of organotypic microenvironments. Co-cultures aim to preserve liver-specific morphology and functionality beyond those provided by cultures of pure parenchymal cells. Stem cells, both embryonic- and adult tissue-derived, may provide a limitless supply of hepatocytes from multiple individuals to improve reproducibility and enable testing of the individual-specific toxicity. This review describes various traditional and novel in vitro liver models and provides a perspective on the challenges and opportunities afforded by each individual test system.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1039/c2tx20051a
