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Cloned Endocrine Cells Transplanted Across Species Function In Host
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WESTPORT, Sep 08 (Reuters) - In the September issue of Nature Medicine, a
research article and three commentaries highlight advances in inter-species
transplantation of cells, tissues and organs.

According to a press release from the journal, publication of these
articles was timed to coincide with the Fourth International Congress on
Xenotransplantation this week in Nantes, France.

In the original research article, Dr. Peter J. Hornsby and colleagues at
Baylor College of Medicine in Houston, Texas, report the successful
transplantation of bovine adrenocortical cells, derived from a single
clone, into adrenalectomized scid mice. Adrenocortical tissue formed by the
transplantation replaced the essential functions of the adrenal glands in
the mice, according to the researchers.

As the mice were immunodeficient there was no immune reaction to the
transplanted cells. The researchers point out that the significance of his
team's research lies in the fact that "...an endocrine tissue, replacing
the host animal's organ, can be derived from a single, normal somatic cell."

"The ability to create xenotransplanted clonal endocrine tissue in host
animals" they continue, "offers the possibility for...genetic manipulation
of the cells before transplantation." Such experiments "...would enable the
resolution of multiple questions in endocrine physiology, cell biology and
molecular biology."

Dr. David H. Sachs of the Massachusetts General Hospital in Boston,
Massachusetts, writes in an accompanying News and Views article, "The fact
that implantation, organization and function of a relatively normal
endocrine tissue occurs in a discordant species when the immune system is
compromised emphasizes the important role that the immune system generally
plays in preventing successful xenotransplantation."

Dr. Sachs acknowledges that, in humans, the immunodeficient state that
permitted success in Dr. Hornsby's mice "...would not be clinically
acceptable" because of inevitable infectious complications.

"For this reason, attempts are underway in our laboratory and elsewhere to
modify the immune response of recipients to xenotransplants through the
induction of specific tolerance to at least some of the most important T
cell stimulatory antigens," he writes. "We have demonstrated that such
tolerance is possible in a highly disparate species combination, pig to
mouse."

In a Commentary article, Dr. Fritz H. Bach and his colleagues at Beth
Israel Deaconess Medical Center in Boston discuss genetic manipulation of
donor animals to protect xenograft recipients against immune reactions.

Rather than systemic administration of immunosuppressive drugs to prevent
xenograft rejection, they suggest "...an alternative approach...involving
suppression of as many rejection factors as possible by genetically
engineering the donor animals and thereby reducing the number of
immunosuppressive agents needed and thus the associated toxicity."

In the fourth paper, Drs. Ole Isacson and Xandra Breakefield of
Massachusetts General Hospital review progress in transplantation of animal
cells into human brains.

Specifically, they discuss the use of fetal pig neurons to replace
dopaminergic neurons in patients with Parkinson's disease and the delivery
of a "suicide gene" to brain tumors in humans via a retrovirus vector
expressed by transplanted mouse fibroblasts.

Clinical trials of both of these techniques are currently underway,
according to the authors.

Dr. Bach spoke with Reuters Health last week shortly before he left for the
Congress in Europe. He summarized the problem that has driven
xenotransplantation research: "There's a tremendous shortage of human
organs for patients who need them." While efforts are made to convince more
people to become donors, "the need is so great that some believe the number
of human donors will not suffice."

Dr. Bach pointed out that while xenotransplantation is intended to benefit
individuals, hazards to the general public must not be overlooked. For
instance, he told Reuters Health, "What the real infectious risk is, nobody
can say, but it's greater than zero, and that's scary."

In the conclusion to their article, he and his colleagues write, "We urge
that individuals considering the transplantation of porcine organs and
cells to humans take into consideration the potential for infectious risk
to the overall population. It seems to us that this factor alone should
discourage such transplants until ... we have more prolonged survival or
porcine organs transplanted orthotopically to nonhuman primates with
documented satisfactory long-term function ... [and] appropriate guidelines
for xenotransplantation."

Nature Medicine 1997;3:944-948,951-952,964-969,978-982.
Copyright 1997 Reuters Limited.
<http://www.reutershealth.com/news/docs/199709/19970908sca.html>
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