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February 18, 2000
 
 
Results Published in journal Science
UNMC Researcher, Colleagues Develop New Cell Transplantation Method That May Help Fight Off  Liver Failure
 
Researchers at Brigham and Women's Hospital (BWH)/Massachusetts Institute of Technology (MIT), along with colleagues at the University of Nebraska Medical Center, Okayama University Medical School in Japan and Genetix Pharmaceuticals have developed a method of genetically manipulating liver cells to help prevent acute organ failure. By temporarily helping to stave off liver failure, the new therapy may allow patients to survive longer for a suitable organ for transplant surgery or for spontaneous recovery of their liver disease.  The findings are published in the Feb. 18 issue of the journal, Science.

“Transplantation of isolated human liver cells has been used in the past in patients with life-threatening liver failure. A major limitation of this form of therapy was the inability to isolate an adequate number of transplantable liver cells” said Philippe Leboulch, M.D., one of the principal investigators and assistant professor at Harvard Medical School and MIT. “We now have devised a gene transfer strategy in which an ‘immortalizing’ gene is introduced into healthy liver cells to allow them to divide actively in culture outside the body.”

Dr. Leboulch said researchers were able to remove the gene permanently so that normal human liver cells could be transplanted in large numbers without the potential danger of keeping the immortalizing gene in the body. This novel procedure is called Reversible Immortalization.”

"The critical need for organ donors continues to force us to look at new ways of solving problems in transplantation," said co-principal investigator, Ira Fox, M.D., associate professor of surgery and a transplant surgeon at the University of Nebraska Medical Center and Nebraska Health System. "This work will hopefully help us develop alternative ways of treating patients with liver failure and, if we're lucky, the technology may apply to the treatment of patients with other medical conditions as well."

Naoya Kobayashi, M.D., first author of the study, now at Okayama University, started the research in Nebraska and then returned to Japan and showed that the reversibly immortalized liver cells were able to function remarkably well after injection in rats with acute liver failure. Whereas all control animals died within three days, 60 percent of the treated animals survived.  The reversibly immortalized human liver cells were able to bridge life in these animals until their own liver could regenerate and take over.

“The liver is the largest and one of the most complex organs in the body,” Dr. Leboulch said. “It converts our food into molecules necessary for life and growth, it produces essential coagulation factors, and it detoxifies and excretes substances that otherwise would be poisonous. For patients who suffer from terminal liver disease, the novel gene transfer strategy of reversible immortalization may one day be a vital bridge of life as they await an organ transplant.”

It is estimated that 25 million Americans are or have been afflicted with liver diseases.  According to the American Liver Foundation, 4,318 liver transplants were performed in 1998.  But because of the shortage of organs, it is estimated that 1,327 patients on the U.S. waiting list died in 1998 while waiting for a liver transplant.

The study was supported by grants from the National Institutes of Health.

UNMC is the only public academic health science center in the state. Through its commitment to research, education, outreach and patient care, UNMC has established itself as one of the country's leading centers for cancer research and treatment, solid organ transplantation and arthritis. Nearly $31 million in research grants and contracts were awarded to UNMC scientists during the past fiscal year. In addition, UNMC’s educational programs are responsible for training more health professionals practicing in Nebraska than any other institution.