Among the organs of the human body, the liver has the highest capacity to regenerate. How the liver manages to repair itself, however, has largely been subject to debate. Now, a new study has revealed a previously unidentified group of cells that can regenerate liver tissue without forming tumors.
These newly discovered cells are better at regenerating tissue than ordinary liver cells, also known as hepatocytes.
Previously, researchers believed that a group of adult stem cells known as oval cells were responsible for the liver’s renowned regenerative properties, but it has since been proven that these stem cells develop into bile duct cells.
Instead, the researchers at the University of California-San Diego School of Medicine have revealed that “hybrid hepatocytes” are behind the liver’s regeneration. Their findings are published in Cell.
“Hybrid hepatocytes represent not only the most effective way to repair a diseased liver, but also the safest way to prevent fatal liver failure by cell transplantation,” says lead author Michael Karin, distinguished professor of pharmacology and pathology.
Cirrhosis – scarring of the liver – can lead to a number of health problems, including enlarged veins in the throat and stomach, jaundice and kidney failure. In the US, the most common causes of cirrhosis are alcoholism and hepatitis – inflammation of the liver.
For the study, the researchers examined the liver cells involved in the regeneration of tissue following injury caused by exposure to an environmental toxin called carbon tetrachloride. They discovered the hybrid hepatocytes in an area of the liver known as the portal triad.
After chronic liver injury, these unique cells proliferate extensively and replenish liver tissue. While they are similar in many ways to regular hepatocytes, they express far lower levels of bile duct cell-specific genes.
“Although hybrid hepatocytes are not stem cells, thus far they seem to be the most effective in rescuing a diseased liver from complete failure,” explains first author Joan Font-Burgada.
At present, many researchers are testing the capabilities of induced pluripotent stem cells (iPSCs) to repair damaged livers and stop liver failure from occurring. Using iPSCs can be difficult, however, as it can be hard to stop these cells from proliferating once they have completed their therapeutic task.
As iPSCs continue to proliferate, the risk of them forming cancerous tumors also increases.
The researchers then tested to see whether the newly discovered hybrid hepatocytes had similar tumor-forming properties by examining tumors in three different mouse models of liver cancer. After failing to find evidence of hybrid hepatocytes in any of the tumors, the researchers concluded that the cells did not contribute to certain forms of liver cancer.
While the majority of the research was conducted using mouse models, the researchers were also able to identify cells similar to the mouse hybrid hepatocytes in human livers.
Experts hope that one day, cell-based therapies will replace the use of liver transplants. Previously, Medical News Today reported on a groundbreaking study in which scientists managed to restore organ function in a live animal’s severely damaged liver by transplanting stem cells grown in a laboratory.
A group of liver stem cells known as hepatic progenitor cells (HPCs) were transplanted into mice and, over the following months, the cells spurred major areas of the liver to regenerate, improving both the structure and the function of the liver.