Stanford University Scientists Identify Source of Liver Stem Cells

Like other tissues that need to replace lost cells, liver has stem cells that both proliferate and give rise to mature cells, even in the absence of injury or disease.

Stanford University scientists have identified stem cells in the liver that give rise to functional liver cells after solving a long-standing mystery about the origin of new cells in the liver.

"We have solved a very old problem by showing that like other tissues that need to replace lost cells, the liver has stem cells that both proliferate and give rise to mature cells, even in the absence of injury or disease," explained lead researcher Roel Nusse, the Howard Hughes Medical Institute (HHMI) investigator at Stanford University.

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The liver is made up mostly of hepatocytes -- highly specialized cells that carry out the organ's many tasks, including storing vitamins and minerals, removing toxins and helping regulate fats and sugars in the bloodstream.

As these cells die off, they are replaced by healthy new hepatocytes but no stem cells had been found in the liver till date. Some scientists speculated that mature hepatocytes might maintain their populations by dividing.

According to Nusse, the mature cells have become so specialized to carry out the work of the liver that they have likely lost the ability to divide.

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"Differentiated liver cells have amplified their chromosomes. This enables the cells to make more proteins, but it really compromises their ability to divide," he informed in a paper appeared in the journal Nature.

Nusse's lab focused on a family of proteins called Wnts, which are key regulators of stem cell fate. Nusse's team discovered that endothelial cells lining the central vein, the blood vessel around which the stem cells were clustered, released Wnt molecules into the tissue.

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Stem cells that migrated out of reach of that signal quickly lost their ability to divide into new stem cells and began to develop into mature hepatocytes. Nusse says this is consistent with how stem cells are known to behave in other tissues.

The team is now investigating how the newly identified stem cells might contribute to regeneration of liver tissue after injury. "It will also be important to explore whether liver cancers tend to originate in these replicating cells, as opposed to more mature hepatocytes," Nusse concluded.

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