Artificial Human Liver Tests New Drugs

Dec. 3, 2007 -- Researchers have developed tiny colonies of living human liver cells that, together, offer a full-sized artificial liver that can be used to screen new drugs before they're sold.

The model could save pharmaceutical companies money in development and, more importantly, reduce health risks in patients.

Last week for example, the UK's Medicines and Healthcare Products Regulatory Agency suspended the license for the arthritis drug Prexige, which was found to cause serious liver reactions in patients. Toxicity is one of the main reasons drugs get pulled off the market.

"If you had a human liver platform outside the body, you could weed out toxic and other problematic compounds much earlier on in the process of drug discovery and development," said postdoctoral associate Salman Khetani of the Harvard-MIT Division of Health Sciences and Technology. "But in order to do robust screening, you need a model system that maintains the physiologic state of the cells," he said.

Khetani and associate professor Sangeeta Bhatia described the technique in a recent issue of the journal Nature Biotechnology.

So far, developing a liver model that resembles the real thing has been a challenge. Researchers typically use liver cells from laboratory rats, which do not always behave like human liver cells. Or they grow human liver cells for tests, but those often do not survive more than a couple of days. Since people usually take drugs over an extended period of time, scientists need a model system that lasts just as long.

Khetani and Bhatia have created an artificial liver that last several weeks.

"To get the human liver cells to live months to years is the next major challenge in this field," said Khetani.

The researchers built the model using the same mass-production technology manufacturers use to etch and assemble the microscopic components on computer chips. But instead of carving out patterns and arranging wires, Khetani's method arranges cells and proteins on a glass or plastic plate.