Document Detail


Hydrogel embedding of precision-cut liver slices in a microfluidic device improves drug metabolic activity.
MedLine Citation:
PMID:  21274846     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A microfluidic-based biochip made of poly-(dimethylsiloxane) was recently reported for the first time by us for the incubation of precision-cut liver slices (PCLS). In this system, PCLS are continuously exposed to flow, to keep the incubation environment stable over time. Slice behavior in the biochip was compared with that of slices incubated in well plates, and verified for 24 h. The goal of the present study was to extend this incubation time. The viability and metabolic activity of precision-cut rat liver slices cultured in our novel microflow system was examined for 72 h. Slices were incubated for 1, 24, 48, and 72 h, and tested for viability (enzyme leakage (lactate dehydrogenase)) and metabolic activity (7-hydroxycoumarin (phase II) and 7-ethoxycoumarin (phase I and II)). Results show that liver slices retained a higher viability in the biochip when embedded in a hydrogel (Matrigel) over 72 h. This embedding prevented the slices from attaching to the upper polycarbonate surface in the microchamber, which occurred during prolonged (>24 h) incubation in the absence of hydrogel. Phase II metabolism was completely retained in hydrogel-embedded slices when medium supplemented with dexamethasone, insulin, and calf serum was used. However, phase I metabolism was significantly decreased with respect to the initial values in gel-embedded slices with medium supplements. Slices were still able to produce phase I metabolites after 72 h, but at only about ∼10% of the initial value. The same decrease in metabolic rate was observed in slices incubated in well plates, indicating that this decrease is due to the slices and medium rather than the incubation system. In conclusion, the biochip model was significantly improved by embedding slices in Matrigel and using proper medium supplements. This is important for in vitro testing of drug metabolism, drug-drug interactions, and (chronic) toxicity. Biotechnol. Bioeng. © 2011 Wiley Periodicals, Inc.
Authors:
Paul M Van Midwoud; Marjolijn T Merema; Niek Verweij; Geny M M Groothuis; Elisabeth Verpoorte
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-18
Journal Detail:
Title:  Biotechnology and bioengineering     Volume:  -     ISSN:  1097-0290     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502021     Medline TA:  Biotechnol Bioeng     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Affiliation:
Pharmaceutical Analysis, Department of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands; tel: +31 50 363 3337, fax: +31 50 363 7582; Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
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