Key points:
- Researchers have created a functional “humanized” liver in living mice.
- Using the model, researchers revealed that liver metabolism is controlled by endothelial cell activity.
- The team says the model can be used immediately by drug companies to assess safety of experimental drugs.
Researchers have found it difficult to study liver disease. Both the mechanisms underlying cholesterol regulation in the liver and potential treatments for chronic liver diseases remain elusive. One major reason for this challenge is that commonly used animal models, such as mice, have livers that perform different functions than those of humans. A new study, published in Cell, has found a solution by creating a complete human liver in a living mouse model.
“Inside the liver, multiple human cell types talk in their own language,” said Richard Flavell, professor at Yale School of Medicine. “Mouse and human cells talk in different languages, but we have enabled human liver cells to speak in their own language within living mice.”
To create this "humanized" liver in mice, Flavell’s team used human liver progenitor stem cells and mature hepatocytes. The humanized liver then developed into the correct shape within the mouse and carried out similar cellular functions as a healthy human liver.
The model has already helped identify human-specific mechanisms for cholesterol level regulation. Researchers found that essential liver metabolism was controlled by endothelial cell activity. These endothelial cells that line blood vessels feeding the liver secrete a signaling molecule called Wnt that regulates cholesterol transport to hepatocytes, which can reduce excess blood cholesterol in humans.
Researchers hope to manipulate cellular function in the humanized liver to better mimic diseases such as human fibrosis and non-alcoholic fatty liver disease. Additionally, the model can be used by drug companies to screen the safety of drugs designed to treat chronic diseases.
“Our long-term goal is to find ways to predict, prevent, and treat all liver diseases, which take such a huge toll on individuals,” the authors said.