Premium
A three‐dimensional microfluidized liver system to assess hepatic drug metabolism and hepatotoxicity
Author(s) -
Corrado Brunella,
Gregorio Vincenza,
Imparato Giorgia,
Attanasio Chiara,
Urciuolo Francesco,
Netti Paolo A.
Publication year - 2019
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26902
Subject(s) - viability assay , spheroid , cytotoxicity , biochip , drug metabolism , chemistry , cell culture , metabolism , biochemistry , cell , pharmacology , biology , bioinformatics , in vitro , genetics
In this study, we propose the design and fabrication of a liver system on a chip. We first chose the most suitable three‐dimensional liver‐like model between cell spheroids and microtissue precursors, both based on the use of hepatocellular carcinoma cells (HepG2) to provide proof‐of‐concept data. Spheroids displayed high cell density but low expression of the typical hepatic biomarkers, whereas microtissue precursors showed stable viability and function over the entire culture time. The two liver‐like models were compared in terms of cell viability, function, metabolism, and the P‐glycoprotein 1 (P‐gp) transport‐protein expression with the microtissue precursors showing the best performance. Thus, we cultured them into a microfluidic biochip featured with three parallel channels shaped to mimic the hepatic sinusoids. To assess the detoxification potential of the microtissue‐loaded biochip we challenged it with a model molecule (ethanol) at different concentrations and time points. Ethanol cytotoxicity was detected by a noninvasive measurement of cell viability based on cell autofluorescence. As expected, a dose‐dependent decrease of albumin and urea secretion was observed in the ethanol‐treated samples. We believe that the described totally human‐derived platform, suitable for integration into a multiorgan microfluidic system, can provide a consistent innovative platform for drug development and toxicity studies.