Laboratory experiments that restored normal function in rats that had lost 90 percent of their livers suggest that the genetic manipulation of cells grown in test tubes could rejuvenate failing liver functions.
The study, to be published in the journal Science, found a way to grow millions of liver cells, called hepatocytes, and then transplant them into rats that had virtually no liver function. The new liver cells took over the job of the failing organ.
``I have no idea when we could use it in humans'' because the technique is still so experimental, said Dr. Philippe Leboulch of Brigham and Women's Hospital, the chief researcher on the study. But he said it offers the promise of one day helping stave off organ failure in patients waiting for a liver transplant.
Leboulch, an assistant professor of medicine at Harvard Medical School, said transplanted liver cells have been used in patients with failing organs before, but the therapy had limited success because doctors were unable to isolate enough liver cells. Hepatocytes are very difficult to grow in the laboratory, he said.
The new technique uses a gene to solve this problem.
Leboulch and his colleagues inserted into laboratory liver cells a cancer gene that forced those cells to start reproducing without limit, a technique known as ``immortalizing.''
Although the cells multiplied by the millions, they could not be transplanted because in the body they would be like a cancer, growing out of control.
To solve this problem, the researchers treated the cells with an enzyme that acts like a ``genetic scissors. It cut out and deactivated the inserted cancer gene, halting the rapid growth of new cells.
The cells were then injected into the spleens of rats whose livers had been 90 percent removed surgically. About 60 percent of these animals lived normally after receiving the genetically engineered cells.
Control animals, which also were missing 90 percent of their livers, did not receive the manipulated cells and died within three days.
``This system may do away with the shortage of hepatocytes,'' Dr. Ira Fox, a co-author of the study, said in Science. ``You could keep (the cells) in the freezer and take them whenever you needed, which is not possible with primary hepatocytes.''
Fox is a liver transplant surgeon at the University of Nebraska Medical Center in Omaha.
Dr. Roy Chowdhury, a liver expert at the Albert Einstein College of Medicine in New York, said in Science that the study results were ``very encouraging,'' but he questioned whether rats with 90 percent of their livers surgically removed represented a true model of human liver failure.
Human liver failure often involves a virus or a toxin that may persist even after the liver cells are transplanted, he said.
About 400,000 of the 20 million Americans with liver disease die annually.
Liver transplants are the only hope for many of these patients, but there only
enough organs to treat about 4,000 patients each year.
InteliHealth Professional Network Clinical Practice.url