A microfluidic hepatic coculture platform for cell-based drug metabolism studies

Eric Novik, Timothy J. Maguire, Piyun Chao, K. C. Cheng, Martin Yarmush

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Within the global pharmaceutical and biotech industries, there is significant interest in identifying in vitro screening systems that are more human-relevant-i.e., that offer greater utility in predicting subcellular and cellular physiological responses in humans in vivo-and that thereby allow investigators to reduce the incidence of costly late-stage failures during pharmaceutical clinical trials, as well as to reduce the use of animals in drug testing. Currently incumbent in vitro screening methods, such as culturing human hepatocytes in suspension, while useful, are limited by a lack of long term cellular function. In order to address this limitation, we have established an integrated, microfluidic, in vitro platform that combines the patented HmREL1 microdevice with a hepatic coculture system. In the present report, we use this platform to study clearance and metabolite generation of a battery of molecular entities. The results show that the flow-based coculture system is capable of clearing, with improved resolution and predictive value, compounds with high, medium, and low clearance values. In addition, when coculture is coupled with flow, higher metabolite production rates are obtained than in static systems.

Original languageEnglish (US)
Pages (from-to)1036-1044
Number of pages9
JournalBiochemical Pharmacology
Volume79
Issue number7
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

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Microfluidics
Coculture Techniques
Metabolism
Metabolites
Liver
Screening
Pharmaceutical Preparations
Drug Industry
Hepatocytes
Suspensions
Animals
Research Personnel
Clinical Trials
Incidence
Testing
In Vitro Techniques
Industry

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Novik, Eric ; Maguire, Timothy J. ; Chao, Piyun ; Cheng, K. C. ; Yarmush, Martin. / A microfluidic hepatic coculture platform for cell-based drug metabolism studies. In: Biochemical Pharmacology. 2010 ; Vol. 79, No. 7. pp. 1036-1044.
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A microfluidic hepatic coculture platform for cell-based drug metabolism studies. / Novik, Eric; Maguire, Timothy J.; Chao, Piyun; Cheng, K. C.; Yarmush, Martin.

In: Biochemical Pharmacology, Vol. 79, No. 7, 01.04.2010, p. 1036-1044.

Research output: Contribution to journalArticle

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