Liver Stem Cell Therapy Holds Promise

Liver damage caused by hepatitis C may eventually be overcome through stem cell therapy.

Hepatitis C patients with liver damage received promising news recently in the form of stem cell research.

According to a new study conducted at the Stanford University School of Medicine, scientists have identified a cell type in the liver of mice that can both self-renew and make new liver cells. The discovery puts to rest many questions that linger about how the organ maintains itself when liver cells, called hepatocytes, grow old and die.

“There’s always been a question as to how the liver replaces dying hepatocytes,” said professor of developmental biology Roel Nusse, PhD. “Most other tissues have a dedicated population of cells that can divide to make a copy of themselves, which we call self-renewal, and can also give rise to the more-specialized cells that make up that tissue. But there never was any evidence for a stem cell in the liver.”

On the contrary, researchers have in the past assumed that mature hepatocytes would themselves divide to replace a dying neighbor. However, this assumption is difficult to prove as the cells have an abnormal amount of DNA, making cell division extremely difficult.

Until now, it was believed that there was just one class of hepatocytes in the liver. Many of these older cells are polyploid, meaning they have more than the normal two copies of each chromosome. While this abundance of chromosomes may make it difficult for cell division, it may lead to other benefits including the enhanced ability to quickly make large amounts of particular proteins.

Rather than being polyploid, the cell population identified by Stanford researchers in the mice is diploid with a normal complement of DNA. They can divide to make copies of themselves or to make cells that start as diploid but then acquire additional copies of their genome as they move out from the central vein into the main body of the liver.

Researchers identified the liver stem cells around the central veins by looking in mice for cells anywhere in the organ that expressed a protein called Axin2. The protein is produced by cells in response to the presence of members of the Wnt signaling protein family. Wnt proteins play a critical role in embryonic development and in the growth and maintenance of stem cells throughout the body, according to the study.

Investigators also found that the endothelial cells that line the interior surface of the central veins in the liver make proteins that confer stem cell properties on local hepatocytes. Additionally, the researchers found that a portion of the descendants of the Axin2-expressing cells move outward from the central vein over a period of time.

The cells become polyploid and begin to express other, hepatocyte-specific genes. After one year, 30 percent of the entire mouse liver was replaced by the descendants and they made up about 40 percent of all hepatocytes in the organ.

While current research was conducted in mice, the possibility that there is more than one kind of hepatocyte in humans could change the face of liver biology forever. Because of this research, there arises an opportunity to better understand human disease.