Mouse given a human liver
Scientists replace the liver cells of mice with human hepatocytes to test novel therapies for human liver diseases.
Tue, Feb 23, 2010 at 05:29 AM
Since certain liver diseases like hepatitis B and C only infect humans and chimpanzees, they can be difficult to study in the lab. But researchers at the Salk Institute have discovered an odd way of getting around the problem. EurekAlert reports that researchers have replaced the liver of a mouse with a human liver, so that the organ can be infected with human liver illnesses and tested for better therapies.
"We found that, not only can we infect our humanized mouse with hepatitis B and hepatitis C, but we can then successfully treat this infection using typical drugs," explained one of the study's authors, Karl-Dimiter Bissig.
Typically when studying diseases and drug therapies that are unique to humans, researchers are able to grow human cells in a dish. But this is impossible with hepatocytes, which are cells involved in protein synthesis and which make up 70 to 80 percent of the cytoplasmic mass of the liver. "Human hepatocytes are almost impossible to work with as they don't grow and are hard to maintain in culture," said senior author Inder Verma.
Usually, the next option for researchers would be to experiment on small lab animals such as mice and rats, but heptatis B and C are host-pathogen specific diseases, meaning that most other animals can't be infected. That's where the chimeric mouse comes in.
In order to completely replace the animal's own liver cells with human ones, the Salk team used a mouse with liver problems of its own. Since the humanized cells were stronger than the mouse's liver cells, the human hepatocytes were able to take hold and populate the mouse liver. The system was then perfected so that 95 percent of the mouse's liver was of human origin.
Once the process was complete, the researchers infected the mouse with both hepatitis B and C. Sure enough, the mouse contracted the diseases. But more importantly, the liver inside the mouse also responded just as a human liver would to standard drug therapies currently used to treat the viruses.
"This shows that our chimeric mouse model is medically relevant and can be used to validate novel drugs in a pre-clinical setting," said Bissig. "This is great news as it provides us with a tool with which we can examine many human hepatotropic pathogens, including malaria."