WASHINGTON, April 4 (Xinhua) -- Liver stem cells that express high levels of telomerase, a protein often associated with resistance to aging, act in mice to regenerate the organ during normal cellular turnover or tissue damage, according to a study by researchers at the Stanford University School of Medicine.
The study, published on Wednesday in the journal Nature, revealed that those cells were distributed throughout the liver's lobes, enabling it to quickly repair itself regardless of the location of the damage.
"It' s critical to understand the cellular mechanism by which the liver renews itself," said Steven Artandi, a professor of medicine. "We've found that these rare, proliferating cells are spread throughout the organ, and that they are necessary to enable the liver to replace damaged cells."
According to Artandi, the paper's senior author, understanding the liver's remarkable capacity for repair and regeneration is a key step in understanding what happens when the organ ceases to function properly, such as in cases of cirrhosis or liver cancer.
"We believe that it is also likely that these cells could give rise to liver cancers when their regulation goes awry," Artandi said.
The liver's cells, called hepatocytes, work to filter and remove toxins from the blood. The liver is unique among organs in its ability to fully regenerate from as little as 25 percent of its original mass.
Artandi's team targeted telomerase expression as a marker to identify the subset of cells responsible for regenerating the liver during normal turnover. They believe those cells could also serve as the cell of origin for liver cancer.
Telomerase is a protein complex that "tops off" the ends of chromosomes after DNA replication. The progressive shortening of telomeres serves as a kind of molecular clock that limits the cells', and, some believe, an organism's, life span.
However, stem cells and some cancer cells make enough telomerase to keep their telomeres from shortening, effectively stopping the aging clock and allowing a seemingly unlimited number of cell divisions.
Mutations that block telomerase activity cause cirrhosis in mice and humans and conversely, mutations that kick telomerase into high gear are frequently found in liver cancers.
Lin Shengda, the paper first author and a postdoctoral scholar at Stanford, found that in mice, about 3 to 5 percent of all liver cells express unusually high levels of telomerase. During regular cell turnover or after the liver was damaged, those cells proliferate in place to make clumps of new liver cells.
"As mature hepatocytes die off, these clones replace the liver mass," said Artandi. "But they are not being recruited away to other places in the liver. This may explain how the liver can quickly repair damage regardless of where it occurs in the organ."
When Lin engineered the telomerase-expressing hepatocytes to die in response to a chemical signal and gave the mice with a liver-damaging chemical, he found that those animals in which the telomerase cells had been killed exhibited much more severe liver scarring than those in which the cells were functional.
Lin told Xinhua that telomerase was a double-edged sword when it came to liver diseases.
Lin said on one hand, telomerase expression allows hepatocytes to continuously regenerate from the daily wear and tear, helping to avoid exhausting the liver's repair capacity, which leads to cirrhosis.
On the other hand, cancer cells undergo unrestricted expansion using the same telomerase when the regeneration process goes bad, according to Lin.