BILLW@SRI-AI.ARPA@sri-unix.UUCP (08/02/83)
From: William "Chops" Westfield <BILLW@SRI-AI.ARPA>
a507 16-Jul-83 23:11
BC-ORGANS-07-16
By Robert Cooke
(c) 1983 Boston Globe (Independent Press Service)
One of the most difficult problems involved in transplanting living
organs - finding suitable matching donors - may soon be overcome,
doctors said Friday.
They said experiments with rats and mice show it is possible to
transplant organs without seeking matching donors, and without
shutting down the recipient's immune system.
''It is believed,'' said Dr. Willyscq Silvers, that if these
techniques can be made to work in humans, then ''transplants may be
accepted with impunity.'' An early suggested human use for the
technique would involve the transplanting of insulin-producing cells
into diabetics.
Silvers added that the specially treated organs transferred between
laboratory animals in his experiments appear to ''take'' even better
than organs transferred into carefully matched recipients.
A professor of human genetics at the University of Pennsylvania
School of Medicine, Silvers delivered his report during a symposium
on transplantation immunogenetics at the Jackson Laboratory in Bar
Harbor, Maine.
''This observation is important,'' Silvers said, ''because it should
increase the number of organs available for transplantation. It is
much easier to locate an unmatched organ than a matched one.''
Also at the symposium was Dr. Paul S. Russell, a kidney transplant
specialists from Massachusetts General Hospital, who cautioned that
''clinical use of this technique requires more refinement.'' But, he
said, ''if it can be accomplished, it would make many more organ
transplants possible.''
Russell noted that if the technique can be developed for use in
human patients, ''it would do away with or lessen the need for''
suppressing the body's immune system to prevent the recipient's body
from rejecting the transplanted organ. Such immunosuppression often
causes major complications through increased susceptibility to
infection.
Dr. Henry Winn, an immunologist at Massachusetts General Hospital,
said: ''I think the rationale is sound. Silvers has excellent data.
There have been disappointments in the past, but I think we'd be
foolish not to try to apply the technique to humans.''
This new approach to organ transplantation revolves around a
discovery that certain cells in the donated organ, called
macrophages, are recognized by the host's body as ''foreign.'' When
an organ is seen as foreign, the body's immune system works to expel
it, similar to the way it attacks invading disease organisms.
Because of this reaction, it is now necessary to select organs from
donors whose tissues appear as compatible as possible with the
recipient's immune system. And doctors often must also use drugs to
turn off the immune system to avoid rejection despite careful
matching of donors and recipients.
''Our evidence indicates,'' Silvers added, ''that if one kind of
cell - the macrophage - is eliminated from the transplant, unmatched
grafts do better than matched ones.
''It seems,'' he said, ''that the recipient only recognizes the
graft in terms of the MHC (major histocompatibility complex, or
surface markers) of its macrophage. When these cells are eliminated,
such grafts cannot be recognized as foreign in mismatch recipients.''
A scientist familiar with Silvers's work, Dr. Jonathan Sprent, a
pathologist at the University of Pennsylvania, said ''the problem,
from a clinical point of view, is that it's not easy to get rid of
these'' macrophage cells from a donated organ. ''It can be done by
culturing certain tissues in vitro (in a laboratory dish) for
prolonged periods, and it has been done in Australia for thyroid or
parathyroid'' gland tissue.
''That's all right for a thyroid or parathyroid in mice, but it's
very difficult to do that in people,'' Sprent said. ''You can't put a
heart in vitro for a month.''
Silvers did note that ''although methods are avilable to eliminate
macrophages from the tissues of mice and rats, these methods need to
be improved to eliminate such cells from human organs. It is believed
if this is accomplished, then transplants may be accepted with
impunity.''
Winn suggested, however, that instead of hearts and kidneys, ''the
first use of this technique might be to transplant healthy
insulin-producing cells of the pancreas into diabetics. .-.-. If this
technique works, then by using the mismatched tissues the disease
would be less likely to recur.''
Sprent said that if insulin-producing cells were the tissue being
transplanted, ''then one could possibly do this.''
END
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