THE liver is the body's "comeback kid", capable of amazing feats of regeneration. But biologists in Pennsylvania have now found that the key to the organ's miraculous ability to repair itself could be cells migrating from bone marrow.
Even if two-thirds of a rat's liver is rem-oved, the organ will grow back to normal size within a week. This incredible regeneration is partly due to the unusual ability of specialised liver cells, or hepatocytes, to keep dividing. But the organ repairs itself even in animals given drugs to prevent this occurring, which shows that other cell types must be involved.
The first clues to the identity of these liver stem cells came in the 1950s, from studies of tumours that grow from another type of cell found in the liver, called oval cells. These cancers contain some cells that look like mature hepatocytes and others that resemble the cells that line the bile duct, which deposits the liver's waste products into the intestine. This suggests that the elusive liver stem cells first give rise to the oval cells, which then divide and differentiate to form hepatocytes and bile duct cells.
Last year, Bryon Petersen and his colleagues at the University of Pittsburgh discovered that oval cells have a "marker" molecule on their surfaces that is also found on haematopoietic stem cells-the cells in our bone marrow that give rise to blood cells. Now, with colleagues at McGill University in Quebec, they have proved that cells from bone marrow can indeed form hepatocytes, bile duct cells and oval cells.
The researchers irradiated mice to des-troy their bone marrow and then replaced it with marrow grafts from other animals whose cells could easily be traced. In one experiment, for example, they gave bone marrow grafts from males to female mice. Then they damaged each animal's liver and waited for it to regenerate. When it had done so, some hepatocytes, oval cells and bile duct cells in the repaired organ clearly contained a male Y chromosome-and so must have been derived from the implanted bone marrow.
"The question of whether there is a liver stem cell has been lingering," says Hyam Leffert of the University of California, San Diego, an expert on liver regeneration. "It's an interesting finding."
The Pittsburgh researchers hope that bone marrow stem cells could be used to grow new liver tissue for patients with cirrhosis. Many groups worldwide are already trying to do this using cultures of dividing hepatocytes.
Author: Nell Boyce
New Scientist issue 1 May 1999
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