High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening

Kwon, Seok Joo; Lee, Dong Woo; Shah, Dhiral A.; Ku, Bosung; Jeon, Sang Youl; Solanki, Kusum; Ryan, Jessica D.; Clark, Douglas S.; Dordick, Jonathan S.; Lee, Moo‐Yeal

doi:10.1038/ncomms4739

Cited by 78 publications

(70 citation statements)

References 43 publications

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“…Reducing these assessments even further, to the cellular level, and relying on only one or two model species to do so is likely an oversimplified approach to screening possible contaminants for environmental risk. HTS screens have utility for toxicological assessment of large numbers of chemicals and have proven useful to detect the most toxic compounds, especially with regards to human health (Forbes and Calow, 2012;Fernandes et al, 2009), and may pinpoint potential toxic mechanisms (George et al, 2011;George et al, 2010;Kwon et al, 2014). In bacteria, HTS assays of membrane integrity can be effective predictors of population growth effects (Priester et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Photosynthetic efficiency predicts toxic effects of metal nanomaterials in phytoplankton

et al. 2017

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a b s t r a c tHigh Throughput Screening (HTS) using in vitro assessments at the subcellular level has great promise for screening new chemicals and emerging contaminants to identify high-risk candidates, but their linkage to ecological impacts has seldom been evaluated. We tested whether a battery of subcellular HTS tests could be used to accurately predict population-level effects of engineered metal nanoparticles (ENPs) on marine phytoplankton, important primary producers that support oceanic food webs. To overcome wellknown difficulties of estimating ecologically meaningful toxicity parameters, we used novel Dynamic Energy Budget and Toxicodynamic (DEBtox) modeling techniques to evaluate impacts of ENPs on population growth rates. Our results show that population growth was negatively impacted by all four ENPs tested, but the HTS tests assessing many cell/physiological functions lacked predictive power at the population level. However, declining photosynthetic efficiency, a traditional physiological endpoint for photoautotrophs, was a good predictor of population level effects in phytoplankton. DEBtox techniques provided robust estimates of EC 10 for population growth rates in exponentially growing batch cultures of phytoplankton, and should be widely useful for ecotoxicological testing. Adoption of HTS approaches for ecotoxicological assessment should carefully evaluate the predictive power of specific assays to minimize the risk that effects at higher levels of biological organization may go undetected.

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Section: Discussionmentioning

confidence: 99%

Photosynthetic efficiency predicts toxic effects of metal nanomaterials in phytoplankton

et al. 2017

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“…To address these limitations, we developed a microfabricated plastic “chip” system capable of 3D cell culture at the nanoliter scale. This platform, which has been described previously for rapid toxicity screening of compounds with human hepatocellular carcinoma cells, consists of two complementary chips that “stamp” together to generate up to 532 independent microscale cultures per chip (Kwon et al., 2014). …”

Section: Introductionmentioning

confidence: 99%

High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform

et al. 2016

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SummaryA 3D cell culture chip was used for high-throughput screening of a human neural progenitor cell line. The differential toxicity of 24 compounds was determined on undifferentiated and differentiating NPCs. Five compounds led to significant differences in IC50 values between undifferentiated and differentiating cultures. This platform has potential use in phenotypic screening to elucidate molecular toxicology on human stem cells.

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“…Kwon et al designed a microchip platform for transducing 3D liver cell cultures with genes for drug metabolism enzymes [11] ( Fig. 2A ).…”

Section: High-throughput Hepatic Systemsmentioning

confidence: 99%

Engineered Liver Platforms for Different Phases of Drug Development

Ware

Khetani

2017

Trends in Biotechnology

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Drug-induced liver injury (DILI) remains a leading cause of drug withdrawal from human clinical trials or the marketplace. Due to species-specific differences in liver pathways, predicting human-relevant DILI using in vitro human liver models is critical. Microfabrication tools allow precise control over the cellular microenvironment towards stabilizing liver functions for weeks. These tools are used to engineer human liver models with different complexities and throughput using cell lines, primary cells, and stem cell-derived hepatocytes. Including multiple human liver cell types can mimic cell-cell interactions in specific types of DILI. Finally, organ-on-a-chip models demonstrate how drug metabolism in the liver affects multi-organ toxicities. In this review, we survey engineered human liver platforms within the needs of different phases of drug development.

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High-throughput and combinatorial gene expression on a chip for metabolism-induced toxicology screening

Cited by 78 publications

References 43 publications

Photosynthetic efficiency predicts toxic effects of metal nanomaterials in phytoplankton

Photosynthetic efficiency predicts toxic effects of metal nanomaterials in phytoplankton

High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform

Engineered Liver Platforms for Different Phases of Drug Development

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