New cell culture system solves problem of growing liver cells.

The complicated organization of the liver's interior is tricky to reproduce in culture.

To study the molecular underpinnings of a disease, scientists often rely on an animal model of the disease or cells grown in a Petri dish. But neither of these methods has shed much light on hepatitis C virus (HCV), which affects the liver. It's exclusively a human disease, so animal models are limited. And liver cells don't survive in typical cell cultures, confounding scientists who want to grow them in the lab.

Now, HHMI investigator Sangeeta Bhatia has designed a workaround: a system that allows liver cells to thrive in the lab. Bhatia, a tissue engineer at the Massachusetts Institute of Technology, creates what she calls “micro-livers” by using computer engineering tools to dot microscopic patterns of liver cells on glass slides.

“Cultured liver cells are very finicky,” says Bhatia. “They're dependent on interactions with other liver cells, and interactions with stromal cells of the liver's connective tissue.” The tools Bhatia developed allow scientists to create an organized environment that lets the cells flourish outside the body.

To test whether HCV could fully infect these liver cultures, Bhatia's lab collaborated with Charles Rice, an HCV expert at Rockefeller University. The team designed an assay in which cells infected with an HCV-like retrovirus were made to fluoresce green when the virus entered. Cells with actively replicating copies of the virus secreted a different light-emitting protein. The researchers showed that liver cells grown in their micro-liver system could be infected with HCV for up to two weeks—enough time to potentially screen drugs or test how the virus behaves inside the cells. The results appeared in the February 16, 2010, issue of the Proceedings of the National Academy of Sciences.

Bhatia's technique for applying organization to liver cell cultures may work for studying other cell types outside the human body—many stem cells, for example, rely on organized systems of multiple cell types to thrive.

“People usually think about tissue engineering for delivering cell therapies to patients,” says Bhatia. “But there's also a benefit to using tissue engineering to develop better in vitro models for drug discovery, ultimately impacting patients with better drugs, not just the delivery of living cells.”

Photo: Don W. Fawcett / Photo Researchers, Inc.