MIT and Rockefeller University Researchers Develop Method for Growing Hepatitis C Virus in Healthy Human Liver Cells

Research on the lifecycle of hepatitis C virus (HCV) and development of effective therapies has been hampered by the fact that the virus is difficult to grow in liver cells in the laboratory; instead, investigators have used "replicon" models or a specific strain of HCV in cancerous liver cells. But now, researchers at the Massachusetts Institute of Technology (MIT) and Rockefeller University have found a way to sustain viral replication for up to 3 weeks in healthy liver cells, as reported in the February 1, 2010 advance online issue of Proceedings of the National Academy of Sciences.

Below is the text of a press release from MIT describing the new advance.

Engineering a New Way to Study Hepatitis C

Advance that could allow scientists to develop and test new treatments for the disease

Cambridge, Mass. -- January 25, 2010 -- Researchers at MIT and Rockefeller University have successfully grown hepatitis C virus in otherwise healthy liver cells in the laboratory, an advance that could allow scientists to develop and test new treatments for the disease.

About 200 million people worldwide are infected with hepatitis C, which can lead to liver failure or cancer, and existing drugs are not always effective. To develop better treatments, researchers need to test them in laboratory experiments in liver cells, but it has been difficult to create a suitable tissue model because healthy liver cells tend to lose their liver functions when removed from the body.

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.

Now, Sangeeta Bhatia, professor in the Harvard-MIT Division of Health Sciences and Technology, in collaboration with Charles Rice of the Rockefeller University, has developed a way to maintain liver cells for four to six weeks by precisely arranging them on a specially patterned plate. 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.

The new model, described in next week's issue of the Proceedings of the National Academy of Sciences, could allow researchers to test the effectiveness of various combinations of drugs, including interferon, a common current treatment, and experimental antibodies that may block the virus from entering cells.

How they did it: The 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. "If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function."

Next steps: The current system may already be suitable to screen drugs against the strain of hepatitis C used in this work; however, this strain, which was derived from a Japanese patient with fulminant hepatitis is the only strain ever successfully grown in a laboratory environment. The researchers hope to modify the system so they can grow additional strains, such as those more common in North America, which would allow for more thorough drug testing.

2/5/10

Reference

A Ploss, SR Khetani, CT Jones, and others. Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures. Proceedings of the National Academy of Sciences USA (Abstract). February 1, 2010 (Epub ahead of print).

Other sources

Massachusetts Institute of Technology. Engineering a new way to study hepatitis C. News release. January 25, 2010.

A Trafton. Engineering a new way to study hepatitis C. MIT News. February 1, 2010.