Researchers at the Massachusetts Institute of Technology (MIT), Rockefeller University and the Medical College of Wisconsin have identified a way to produce liver-like cells from induced pluripotent stem cells (iPSCs), which are made from body tissues rather than embryos; the liver-like cells can then be infected with hepatitis C.
Such cells could enable scientists to study why people respond differently to the hepatitis C infection.
In 2011, Sangeeta Bhatia, professor of electrical engineering and computer science at MIT, and Charles Rice, a professor of virology at Rockefeller, reported that they could induce liver cells to grow outside the body by growing them on special micropatterned plates that direct their organization.
These liver cells can be infected with hepatitis C, but they cannot be used to proactively study the role of genetic variation in viral responses because they come from organs that have been donated for transplantation and represent only a small population.
To make cells with more genetic variation, Bhatia and Rice decided to team up with Stephen Duncan, a professor of human and molecular genetics at the Medical College of Wisconsin, who had shown that he could transform iPSCs into liver-like cells.
Such iPSCs are derived from normal body cells, often skin cells. By turning on certain genes in those cells, scientists can revert them to an immature state that is identical to embryonic stem cells, which can differentiate into any cell type. Once the cells become pluripotent, they can be directed to become liver-like cells by turning on genes that control liver development.
In this study, MIT postdoc Robert Schwartz and graduate student Kartik Trehan took those liver-like cells and infected them with hepatitis C. To confirm that infection had occurred, the researchers engineered the viruses to secrete a light-producing protein every time they went through their life cycle.
The researchers’ ultimate goal is to take cells from patients who had unusual reactions to hepatitis C infection, transform those cells into liver cells and study their genetics to see why they responded the way they did. “Hepatitis C virus causes an unusually robust infection in some people, while others are very good at clearing it. It’s not yet known why those differences exist,” Ms Bhatia says.
One potential explanation is genetic differences in the expression of immune molecules such as interleukin-28, a protein that has been shown to play an important role in the response to hepatitis infection. Other possible factors include cells’ expression of surface proteins that enable the virus to enter the cells, and cells’ susceptibility to having viruses take over their replication machinery and other cellular structures.
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