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The Current Status of Alternatives to Animal Testing and Predictive Toxicology Methods Using Liver Microfluidic Biochips

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Abstract

In this paper, we will consider new in vitro cell culture platforms and the progress made, based on the microfluidic liver biochips dedicated to pharmacological and toxicological studies. Particular emphasis will be given to recent developments in the microfluidic tools dedicated to cell culture (more particularly liver cell culture), in silico opportunities for Physiologically Based PharmacoKinetic (PBPK) modelling, the challenge of the mechanistic interpretations offered by the approaches resulting from “multi-omics” data (transcriptomics, proteomics, metabolomics, cytomics) and imaging microfluidic platforms. Finally, we will discuss the critical features regarding microfabrication, design and materials, and cell functionality as the key points for the future development of new microfluidic liver biochips.

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Abbreviations

3T3:

Mouse fibroblast cell line

A549:

Human lung alveolar carcinoma cell line

ADME:

Absorption, Distribution, Metabolism and Excretion

APAP:

Acetyl-P-AminoPhenol (acetaminophen)

CEFIC:

Conseil Européen des Industries Chimiques

CYP:

Cytochromes P450

EROD:

Ethoxy Resorufin O Deethylase

GSEA:

Gene Set Enrichment Analysis

GSH:

Glutathione

HCS:

High Content Screening

HCT-116:

Human colon carcinoma cell line

Hep3B:

Human hepatoma cell line

HepaRG:

Hepatoma-derived cell line

HepG2/C3a:

Human liver hepatocarcinoma cell line/subclone C3a

HK-2:

Renal tubular proximal cell line

HPA:

Primary human preadipocyte

IC50:

Inhibition Concentration of 50% of the analysed endpoints

KEGG:

Kyoto Encyclopedia of Genes and Genomes

LD50:

Lethal dose leading to the death of 50% of population

MCF7:

Human breast adenocarcinoma cell line

MDCK:

Madin Darby Canine Kidney cell line

MDR1:

Multi Drug Resistance 1 (P-glycoprotein 1)

MRP2:

Multi drug resistant associated protein number 2 gene

MS:

Mass spectrometry

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NAPQI:

N-Acetyl-P-Benzoquinone Imine

NMR:

Nuclear Magnetic Resonance spectrometry

PBPK:

Physiologically Based PharmacoKinetic

PDMS:

Polydimethylsiloxane

PK-PD:

PharmacoKinetic-PharmacoDynamic

REACH:

Registration, Evaluation and Authorization of Chemicals

SULT:

Sulfo-transferase

UGT:

UDP-glucuronyltransferase

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Acknowledgments

Jean Matthieu Prot received a grant from the post grenelle 189 project “Activism”. The UTC liver microfluidic biochips project is supported by the foundation of the University of Technology of Compiègne “La Fondation UTC pour l’innovation” via the “puce à cellule” project. The project was also supported by the ANR PCV 2007 program via the “μHepaReTox” project and by the ANR CP2D 2007 program via the SysBioX project. Finally, we thank Frederic Bois and Céline Brochot for their help in the discussion-redaction of the review.

Conflict of interest

We declare to have no conflict of interest.

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  1. CNRS UMR 6600, Laboratoire de Biomécanique et Bioingénierie, Université de Technologie de Compiègne, Compiègne, France

    Jean Matthieu Prot & Eric Leclerc

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  2. Eric Leclerc
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Correspondence to Eric Leclerc.

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Associate Editor Michael Shuler oversaw the review of this article.

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Prot, J.M., Leclerc, E. The Current Status of Alternatives to Animal Testing and Predictive Toxicology Methods Using Liver Microfluidic Biochips. Ann Biomed Eng 40, 1228–1243 (2012). https://doi.org/10.1007/s10439-011-0480-5

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  • DOI: https://doi.org/10.1007/s10439-011-0480-5

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