Liver toxicity is one of the main reasons pharmaceutical companies pull drugs off the market. These dangerous drugs slip through approval processes due in part to the shortcomings of liver toxicity tests. Existing tests rely on liver cells from rats, which do not always respond to toxins the way human cells do.
The new technology arranges human liver cells into tiny colonies only 500 micrometers in diameter that act much like a real liver and survive for up to six weeks.
Sangeeta Bhatia, associate professor in the Harvard-MIT Division of Health Sciences and Technology (HST) and MIT's Department of Electrical Engineering and Computer Science, and HST postdoctoral associate Salman Khetani
To build these model livers, postdoctoral associate Salman Khetani uses micropatterning technology — the same technology used to place tiny copper wires on computer chips — to precisely arrange human liver cells and other supporting cells on a plate.
Such precisely arranged cells results in what Sangeeta Bhatia, associate professor in the Harvard-MIT Division of Health Sciences and Technology (HST) calls a “high-fidelity tissue model” because it so closely mimics the behavior of a human liver. For example, each model “organ” secretes the blood protein albumin, synthesizes urea, and produces the enzymes necessary to break down drugs and toxins.
To predict how close their model tissue is to real liver tissue, which has over 500 different functions, they also evaluated its gene expression profiles, measures of the levels of gene activation in the tissues. They found that these profiles are very similar to those of fresh liver cells, “giving us confidence that other [liver] functions are preserved,” said Khetani.
For drug testing purposes, this affinity to the human liver allows each colony to provide a window into the human liver’s response to a drug without having to expose human patients to the drug in a clinical trial, said Bhatia.
MEDICA.de; Source: Massachusetts Institute of Technology