In a major innovation in organ transplantation that could offer hope
to millions of Americans with organ failure or diabetes, a study by Ximerex
, Inc. in conjunction with researchers from the University of Nebraska
Medical Center has demonstrated that acute rejection of pig heart transplants
could be prevented without the need for severe immune suppression.
The findings were reported in the February issue of the Annals of Surgery.
Most candidates for an organ transplant do not receive one because of
a severe shortage of human organ donors. Pig organ transplants (xenografts)
could solve the problem, but scientists have been frustrated in their efforts
to prevent rejection. With current technology, severe immune suppression
would be required, leaving the recipient vulnerable to infection.
Our findings represent a key step towards ultimately being able to
use pig organs in humans with organ failure or diabetes, said William
E. Beschorner, M.D., founder and president of Ximerex (KI-MER-ex), Inc.
and an adjunct professor of surgery at the University of Nebraska Medical
Center. In addition to heart transplants, the technology developed in
this study would also be applicable to kidney, liver and pancreatic islet
cell transplants.
In the study, 13 experimental sheep received heart grafts from pigs
containing sheep cells. Only one developed acute vascular rejection typical
of pig xenograft rejection. Five developed a milder form of rejection,
cellular rejection, which responded to steroid therapy. Cellular rejection
is typically seen following a human-to-human organ transplant. The remaining
seven sheep, followed for up to 70 days, never developed significant rejection.
The recipient sheep experienced minimal complications and retained their
ability to fight infections.
In contrast, all 12 of the control sheep, transplanted with heart grafts
from pigs not containing sheep cells, rejected their grafts by acute vascular
rejection in four to eight days, even though they received the same immune
suppression.
The key to this breakthrough was the transfusion of bone marrow cells
from the recipient sheep into the donor pigs during fetal development.
After the pigs were born, white cells from the pigs spleen, containing
both sheep and pig cells were transfused into the recipient sheep, followed
by the heart transplant. Modest immune suppression was given, less than
that given for a human receiving a human heart transplant.
Dr. Beschorner, senior author of the study, said growing the patients
cells within the donor pig accomplishes the major goals of transplantation
within the donor pig, before performing the transplant.
The fetal pig environment is ideal for the growth of cells from another
species. It also is ideal for the development of immune tolerance and tissue
accommodation, he said. The patients cells learn to ignore the pig tissues.
The donor pig tissues become adapted to resist injury by antibodies against
pig tissues. The dilemma in xenotransplantation has been that pig organs
are very different from human organs, triggering severe rejection reactions.
How do you block these reactions and leave the patients immune system
intact? Our method of transplanting the donor pig gets us past this roadblock.
Before our new technology can be tested in human recipients, we need
to do the appropriate studies in non-human primates. Those could prove
more challenging than our study in sheep. However, we have successfully
grown human cells in fetal pigs, so we are optimistic about the non-human
primate transplant studies.
Dr. Beschorner said the primate studies would take one to two years.
Funds to support these trials must first be obtained.
Each year 750,000 Americans die of heart failure. The International
Society of Heart and Lung Transplantation estimates that 50,000 lives could
be saved with heart transplants. However, due to the shortage of donor
organs, only about 2,200 transplants are performed.
It is estimated that if xenotransplantation were as effective as human
organ transplantation, 500,000 Americans could be helped each year. In
the developed world, as many as 1.3 million patients could be helped annually.
The average reimbursement rate for procuring a human organ is about $25,000.
At this rate, the potential market would be about $32 billion.
Dr. Beschorner is an experimental pathologist and has been studying
the problems associated with organ transplantation for more than 25 years.
His early studies in this field were done at the Johns Hopkins Hospital
in Baltimore, Md. He relocated to Nebraska in 1997.