In vitro models for liver toxicity testing

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. Imm...

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Main Authors: Soldatow, Valerie Y., LeCluyse, Edward L., Griffith, Linda G., Rusyn, Ivan
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Royal Society of Chemistry 2014
Online Access:http://hdl.handle.net/1721.1/88931
https://orcid.org/0000-0002-1801-5548
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author Soldatow, Valerie Y.
LeCluyse, Edward L.
Griffith, Linda G.
Rusyn, Ivan
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Soldatow, Valerie Y.
LeCluyse, Edward L.
Griffith, Linda G.
Rusyn, Ivan
author_sort Soldatow, Valerie Y.
collection MIT
description 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.
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spelling mit-1721.1/889312022-10-01T14:22:52Z In vitro models for liver toxicity testing Soldatow, Valerie Y. LeCluyse, Edward L. Griffith, Linda G. Rusyn, Ivan Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Griffith, Linda G. 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. National Institutes of Health (U.S.) (P42 ES005948) National Institutes of Health (U.S.) (R01 ES01524) 2014-08-20T16:26:24Z 2014-08-20T16:26:24Z 2013 2012-07 Article http://purl.org/eprint/type/JournalArticle 2045-452X 2045-4538 http://hdl.handle.net/1721.1/88931 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. https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1039/c2tx20051a Toxicology Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Royal Society of Chemistry PMC
spellingShingle Soldatow, Valerie Y.
LeCluyse, Edward L.
Griffith, Linda G.
Rusyn, Ivan
In vitro models for liver toxicity testing
title In vitro models for liver toxicity testing
title_full In vitro models for liver toxicity testing
title_fullStr In vitro models for liver toxicity testing
title_full_unstemmed In vitro models for liver toxicity testing
title_short In vitro models for liver toxicity testing
title_sort in vitro models for liver toxicity testing
url http://hdl.handle.net/1721.1/88931
https://orcid.org/0000-0002-1801-5548
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