Mimicking the human liver

Despite the wealth of in silico designs and in vitro assays that scientists use to identify new therapeutic compounds, a new drug often fails because of side effects noted during in vivo screening.

Randall C Willis
DURHAM, N.C.—Despite the wealth of in silico designs and in vitro assays that scientists use to identify new therapeutic compounds, a new drug often fails because of side effects noted during in vivo screening. Thus, while in vivo screening can be expensive, it is irreplaceable—unless, of course, someone can find a way to mimic in vivo metabolism in vitro. With this in mind, researchers at ADMET Technologies and the University of North Carolina recently created an artificial liver.
 
As they described recently in a poster, the researchers developed a multicoaxial bioreactor (MCB) that is based on 2-D sandwich cell culturing techniques developed decades ago. In this case, however, the hepatocytes grow in a three-dimensional matrix that more closely mimics the structure and dimensions of a human liver. Thus, when drugs are introduced to the MCB, it is thought their behavior more closely follows physiological pharmacokinetics.
 
The scientists isolated liver cells, which they introduced to a 50:50 mixture of collagen type 1 and Matrigel, allowing the combination to gel in the MCB. They then used NMR spectrometry to monitor metabolic activity and noted that the MCB cells behaved as expected and that enzyme levels and general cell health remained constant over an extended period of time. And in each case, the cells in the 3-D matrix performed more naturally than those in a 2-D sandwich.

Randall C Willis

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