Annals of Biomedical Engineering

, Volume 40, Issue 6, pp 1228–1243 | Cite as

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

Article

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.

Keywords

Liver Microfluidic biochips PBPK models Transcriptomics Proteomics Metabolomics Cytomics Alternative methods Predictive toxicology 

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

Notes

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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Copyright information

© Biomedical Engineering Society 2011

Authors and Affiliations

  1. 1.CNRS UMR 6600, Laboratoire de Biomécanique et BioingénierieUniversité de Technologie de CompiègneCompiègneFrance

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