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Drug Discov Today. 2011 May;16(9-10):382-97. doi: 10.1016/j.drudis.2011.02.012. Epub 2011 Feb 24.

Improved preclinical safety assessment using micro-BAL devices: the potential impact on human discovery and drug attrition.

Author information

1
Centre for Biotechnology and Biomedicine, Department of Cell Techniques and Applied Stem Cell Biology, University of Leipzig, Deutscher Platz 5, D-04103 Leipzig, Germany. giri.shibashish@bbz.uni-leipzig.de

Abstract

Hepatotoxicity is often unpredictable in the early phase of drug discovery and leads to drug attrition in preclinical and clinical development. Here, we discuss the conventional preclinical liver models that do not mimic in vivo livers. We focus on key components such as new sources of hepatocyte-derived human stem cells, enhanced direct oxygenation, defined biocompatibility nanoscaffolds, organotypical cellular models, dynamic culture, and metabolite status inside and outside the cell for effective configuration for the development of a bioartificial liver (BAL) device to mimic the in vivo liver microenvironment. The potential for development of BAL devices could open up new avenues in: (i) hepatotoxicity assessment for selecting drug candidates during preclinical screening; and (ii) therapeutic approaches for liver cell therapy at the clinical stage.

PMID:
21354326
DOI:
10.1016/j.drudis.2011.02.012
[Indexed for MEDLINE]

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