Microscale culture of human liver cells for drug development
PUBLICATION TYPE:
Journal Article
AUTHORS:
Khetani, S., Bhatia, S.
SOURCE:
Nature Biotechnology 26, 120–126 (2008). https://doi.org/10.1038/nbt1361
URL:
https://www.nature.com/articles/nbt1361
ABSTRACT:
Tissue function depends on hierarchical structures extending from single cells (∼10 μm) to functional subunits (100 μm–1 mm) that coordinate organ functions. Conventional cell culture disperses tissues into single cells while neglecting higher-order processes. The application of semiconductor-driven microtechnology in the biomedical arena now allows fabrication of microscale tissue subunits that may be functionally improved1 and have the advantages of miniaturization2. Here we present a miniaturized, multiwell culture system for human liver cells with optimized microscale architecture that maintains phenotypic functions for several weeks. The need for such models is underscored by the high rate of pre-launch and post-market attrition of pharmaceuticals due to liver toxicity3. We demonstrate utility through assessment of gene expression profiles, phase I/II metabolism, canalicular transport, secretion of liver-specific products and susceptibility to hepatotoxins. The combination of microtechnology and tissue engineering may enable development of integrated tissue models in the so-called 'human on a chip'4.
