Bhatia team's microliver research reveals how to target hepatitis C

February 2, 2010

Liver cells in a micropatterned co-culture form tube-like structures (shown here in green) that resemble bile capillaries found in a human liver.  Image courtesy of Sangeeta Bhatia lab, MIT

Sangeeta Bhatia, professor of electrical engineering and computer science at MIT and in the Harvard-MIT Division of Health Sciences and Technology has headed a team including Charles Rice of Rockefeller University, to develop a method for growing hepatitis C virus in liver cells that can be maintained for up to four to six weeks. The team's work has been reported in recent papers published this week Feb. 1, 2010 in the Proceedings of the National Academy of Sciences and Nature Biotechnology.

As reported by the MIT News Office on Feb. 1, 2010 hepatitis C, a virus that can cause liver failure or cancer, infects about 200 million people worldwide. Existing drugs are not always effective, so many patients end up on long liver-transplant waiting lists.

One reason that no better treatment options exist is the lack of a suitable liver tissue model to test new drugs in the laboratory. In the new tissue model, liver cells are precisely arranged on a specially patterned plate and surrounded by supportive cells, allowing them to live and function for four to six weeks. (See the MIT News November 19, 2007 article "Micro livers could aid drug screening"). The cells can be infected with hepatitis C for two to three weeks, giving researchers the chance to study the cells’ responses to different drugs.

“With this model system, one can study hepatitis C and its chronic effects in greater mechanistic detail,” says Salman Khetani, former MIT postdoctoral associate and an author of two recent papers on the work. “Since it uses normal human liver cells rather than cancer-derived ones, our system may provide a better understanding of how hepatitis C progresses in humans, and of potential cures.”

Previously, researchers have been able to induce cancerous liver cells to survive and reproduce outside the body, but those cells are not sufficient for studying hepatitis C because their responses to infection are different from those of normal liver cells.

To create their new model, researchers used healthy liver cells that had been cryogenically preserved and grew them on special plates with micropatterns that direct the cells where to grow. The liver cells were strategically interspersed with other cells called fibroblasts that support the growth of liver tissue.

“If you just put cells on a surface in an unorganized way, they lose their function very quickly,” says Bhatia, who is also a Howard Hughes Medical Institute Investigator. “If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.”