Yale researchers create “humanized” liver in living mice to review chronic liver diseases

Yale researchers have created a functional “humanized” liver in living mice that can help scientists find human-specific mechanisms for regulating levels of cholesterol and potentially for treating chronic liver diseases afflicting tens of thousands and thousands of individuals in the US.

The findings are published Aug. 9 within the journal Cell.

Chronic liver diseases similar to alcoholic and non-alcoholic liver disease, cancer, viral hepatitis, fibrosis, and cancer affect greater than 1.5 billion people worldwide. Within the U.S., an estimated 30 to 40% of the population has been diagnosed with non-alcoholic fatty liver disease alone. Yet liver disease has been difficult to review in animal models. The livers of mice, as an illustration, perform different functions than those of humans.

Contained in the liver multiple human cell types talk in their very own language. Mouse and human cells talk in several languages, but we have now enabled human liver cells to talk in their very own language inside living mice.”

Richard Flavell, Senior Writer, Sterling Professor of Immunobiology at Yale School of Medicine and investigator for the Howard Hughes Medical Institute

For the study, a team of scientists led by Eleanna Kaffe, an associate research scientist in Flavell’s Lab, used progenitor stem cells and mature cells generally known as hepatocytes from a human liver to create a whole human liver in a mouse model. The humanized liver, researchers said, developed into similar size-adjusted shape and carried out similar cellular functions as a healthy human liver. The cellular functions within the humanized liver may be manipulated to mimic human fibrosis and non-alcoholic fatty liver disease, the researchers report.

The researchers also found that essential liver metabolism is controlled by activity in endothelial cells, which line blood vessels that feed the liver. Those endothelial cells, they said, secrete a signaling molecule called Wnt which regulates cholesterol transport to hepatocytes for the synthesis of bile acid. The transport of cholesterol to hepatocytes is a crucial mechanism that reduces excess blood levels of cholesterol in humans.

In accordance with the researchers, the humanized liver model will be used immediately by drug firms in search of to evaluate safety of experimental drugs designed to treat chronic diseases.

“Nevertheless, our long-term goal is to search out ways to predict, prevent, and treat all liver diseases, which take such an enormous toll on individuals,” the authors said.