Clue To Creating Liver Cells

Special bone marrow cells have been shown to convert into basic liver tissue, raising the possibility of one day using a patient's own marrow to repair failing livers, researchers say.

In laboratory rat studies at the University of Pittsburgh Medical Center, researchers found in bone marrow a master, or stem, cell that under special conditions will convert itself into functioning liver tissue cells.

Bryon Petersen, lead author of the study to be published Friday in the journal Science, said the work is the first step toward learning how to rescue failing livers using the body's own stem cells.

Petersen said that in new experiments he already has shown that injecting the special marrow cells into rats causes the animals to form new liver tissue.

Although the work only has been demonstrated in laboratory animals, Petersen said other studies strongly suggest humans also have bone marrow cells that will convert into liver cells. "What we have learned from the rat, we should be able to extrapolate to the humans," said Petersen. But he cautioned that perfecting the technique for humans might take a decade.

Dr. John M. Vierling, liver specialist at Cedars-Sinai Medical Center in Los Angeles and chairman of the board of the American Liver Foundation, said the research raises "very exciting" possibilities for reviving dying livers.

Vierling said that other researchers have been trying with little success to find in the liver stem cells that could make new tissue. If the cells can be isolated from the bone marrow and cultured raises the possibility of finding a virtually unlimited supply of key liver cells. "The ability to take something from scratch, so to speak, and grow it up in the quantity that you need would be extraordinary," Vierling said.

Dr. Mark F. Pittenger, a researcher at Osiris Therapeutics in Baltimore who recently found in bone marrow the stem cells for bone, cartilage and fat, called Petersen's findings "a significant step forward."

"It bodes well for our learning how to regenerate organs," said Pittenger. "Liver disease is a very serious problem."

The American Liver Foundation says about 26,000 Americans die annually from liver disease. About 5 million in the U.S. are infected with hepatitis B or C, a viral disease that is a major cause of liver failure.

Petersen said that his research investigated how some people with liver failures are able to grow new liver tissue. Some patients with failing livers recover after the organ spontaneously grows new cells.

The liver often can generate new hepatocytes, or a type of healthy liver cells, after an injury or disease. But Petersen said that some patients who do not make new hepatocytes still end up growing new liver tissue and recovering.

Just how this happens has long been a mystery. Researchers suspected special cells in the bone marrow somehow were prompted to start making new cells for the distressed organ Peterson said research using the lab rats proves that bone marrow is the source of these new liver cells.

In the study, Petersen and his colleagues destroyed the bone marrow of female rats and replaced it with marrow from male rats. This meant that the female rats had bone marrow that carried the male Y chromosome, which could be used to identify cells.

The scientists treated the female rats with a chemical that prevented their livers from regenerating and then damaged the livers, mimicking an injury.

Two weeks later, the livers were removed and the researchers found they contained new liver cells that carried the Y chromosome marker. This meant that cells from the bone marrow had gone to the failing livers and started the regeneration process. "This suggests that there is a stem cell in the adult bone marrow that is capable of becoming anything if you give it the right signal," said Petersen. "I have been able to show that there is a cell in the bone marrow for the liver."

Petersen said that once researchers learn to isolate stem cells from the bone marrow, switch them into liver cells, and then grow them into large quantities, it might be possible to rescue failing livers with simple injections.

Vierling cautioned, however, that the technique would not totally replace the need for liver transplants.