New Model For Treatment Of Liver Disease
How do you study-and try to cure in the laboratory-an infection that only humans can get? A team led by Salk Institute researchers does it by generating a mouse with an almost completely human liver.
This "humanized" mouse is susceptible to human liver infections and responds to human drug treatments, providing a new way to test novel therapies for debilitating human liver diseases and other diseases with liver involvement such as malaria.
"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," explains first author Karl-Dimiter Bissig, M.D. Ph.D, an internist and post-doctoral researcher in the Laboratory of Genetics.
"As a physician, I understand the importance of this type of bench-to-bedside research. This study shows a real application for our mouse model, making it relevant from both an academic and a clinical perspective."
Host-pathogen specificity is both a blessing and a curse-preventing widespread infection but making successful treatments harder to find. For example, Hepatitis B and Hepatitis C can only infect humans and chimpanzees, and although this species barrier prevents us from being susceptible to every infection out there, the flipside is that finding treatments for human infections can be extremely difficult.
This is particularly true when it comes to liver infections. The usual approach is to grow human cells in a dish, to infect and try to treat them there, but this is not possible with liver cells or hepatocytes. "Human hepatocytes are almost impossible to work with as they don't grow and are hard to maintain in culture," explains senior author Inder Verma, Ph.D., a professor in the Laboratory of Genetics and holder of the Irwin and Joan Jacobs Chair in Exemplary Life Science.
And since small animals cannot be infected with Hepatitis C, they cannot be used to test drugs that may cure this disease. What's more, species differences mean that drugs that appear to be effective and non-toxic in animal models sometimes prove to be toxic to humans, and vice versa. Mice whose own hepatocytes have been replaced with human liver cells provide a solution to all these hurdles.
"Mice whose own liver cells have been replaced with human hepatocytes (shown in green) can be successfully infected with hepatitis B virus (shown in red) providing a new way to test novel therapies for debilitating human liver diseases. (Credit: Courtesy of Dr. Karl-Dimiter Bissig, Salk Institute for Biological Studies)"
Source: Salk Institute
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