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, UNMCs educational
programs are responsible for training more health professionals practicing
in Nebraska than any other institution.