Doctors Advance in Helping Body to Repair Itself
Hi all,
This is an old article that relates to Dr. Faustman’s research which
is currently being funded by the Lee Iacocca foundation through
donations. It is interesting and explains how they came upon this
discovery. It does mention that she does not know where the new
islet cells came from but since this article, Dr. Faustman has
discovered the spleen does play a role in it.
(FYI: This research does not use embryonic stem cells & the clinical
trials have been approved by the FDA)
Hope you find it interesting and if you are interested in getting
involved, please visit: “joinleenow.org”.
Happy 4th to all of you ! Evelyn 
January 15, 2002
Doctors Advance in Helping Body to Repair
Itself
By GINA KOLATA
Enshrined in textbooks, taught in schools and rarely questioned was
one truism of medicine: the only organs that can regenerate their
cells are the bone marrow, the liver and, maybe, the kidney.
But now, researchers say, they are not so sure. To their
astonishment, scientists at Harvard Medical School recently
discovered that in mice, the insulin- producing cells of the pancreas
could regenerate. Other experts, at New York Medical College, just
reported compelling evidence that human hearts can grow new cells.
The findings have enormous implications, scientists say, although it
can be a long and harrowing path from observations like these to
medical treatments. The encouraging news is that the body has an
unappreciated capacity to repair itself. But in making that
discovery, researchers also found a potential therapeutic stumbling
block: an underlying disease, like diabetes, which kills
pancreas cells, may outpace the regeneration of those cells. Even
adding new cells, like ones derived from sources like stem cells, may
be futile. To regenerate tissues and organs, it may be necessary
first to cure an underlying disease. Nonetheless, some medical
experts are optimistic. “These are really intriguing results,” said
Dr. Gregory Stock, who directs the program on medicine, technology
and society at the University of California at Los Angeles School
of Medicine. The results show that “there may be ways of eliciting
responses from the body that we would not have dared to look for,” he
said. That, however, was furthest from the minds of the scientists
who chanced upon regeneration of pancreas cells in mice.
The work began, said Dr. Denise Faustman, a diabetes researcher at
Harvard, because she was trying to get around a fundamental obstacle
to curing Type 1 diabetes. The disease usually occurs in puberty and
afflicts an estimated half-million to a million Americans. It occurs
because islet cells, the insulin-producing cells of the pancreas,
die, almost always because they are attacked by cells of the
immune system. But the underlying disease that killed those cells
also seems to kill any that are transplanted to replace them.
The problem had become clear in mice. Scientists created diabetes by
destroying the animals’ islet cells and then, with ease, cured the
disease by transplanting new ones. But, they found, transplants did
not work in another strain of mice whose diabetes more closely
resembled the human disease, caused when their immune systems
attacked and killed the islet cells. Despite islet cell transplants,
the mice remained diabetic.
Nonetheless, doctors have spent decades trying to cure severe
diabetes by giving patients new pancreases or new islet cells, with
generally dismal outcomes, said Dr. David M. Nathan, who directs the
diabetes center at Massachusetts General Hospital. The best results
by far are from a small study by scientists at the University of
Alberta in Edmonton, Canada, who transplanted islet cells to patients
with severe diabetes and used a new regimen of drugs to suppress the
immune systems.
Their initial report, nearly two years ago, was that all eight
patients who had the transplants no longer had diabetes. Last year,
they published an update, on a total of 12 patients who had islet
cell transplants. Four no longer had any signs of diabetes
their
blood sugar levels were normal. In five patients, blood sugar levels
were elevated, an indication that the islet cells were not
fully functioning. And in three, diabetes had returned.
The work is continuing, at Edmonton and at other medical centers,
including Massachusetts General, and Dr. Edmond A. Ryan at the
University of Alberta said he remained optimistic. “It’s going well,
but it’s not perfect,” he said. Others are less enthusiastic.
Dr. Nathan said he was now convinced that without stopping the
underlying disease, “there is no reason to think the diabetes will
not return.” So Dr. Faustman set out to find a way to suppress the
immune system’s attack, thinking she could then successfully
transplant islet cells into naturally diabetic
mice.
After years of work, she and her colleagues hit on a method that
worked. It involved training immune system cells in the blood not to
attack islet cells and, at the same time, killing immune system cells
in the pancreas where an attack on islet cells was under way. It was
time for what the researchers thought would be the ultimate test.
First they would stop the underlying diabetes with their new method.
Then they would transplant islet cells into the mice. And, to prove
that the cells had cured the mice, they would take the transplanted
cells out and watch the diabetes return. Since it is impossible to
pluck transplanted islet cells from a mouse’s pancreas, the
researchers slipped the new cells into one animal’s kidneys. The
cells would secrete insulin, just as they would if they were in the
pancreas, controlling the diabetes. That way, they could later remove
the kidney and take out the islet cells with it. That, at least, was
the plan.
At first, the experiment seemed to be a huge success the mice
were
cured of their diabetes. “We were very proud of ourselves,” Dr.
Faustman said. Then the scientists removed the kidneys containing the
islet cells. To their astonishment, it made no difference the
animals still made their own insulin and no longer had diabetes. “I
said, `Oh no how could this have happened?’ ” Dr. Faustman
said. “We moped around.” Finally, it occurred to them that maybe the
experiment was not a failure. Maybe the islet cell transplant was not
necessary because once the scientists blocked the underlying disease,
the pancreas could regenerate its own islet cells.
“It was a total surprise it knocked our socks off,” Dr. Nathan
said.
Dr. Faustman says she still does not know where the new islet cells
came from. They may have grown from pancreas cells. Or they may have
come from immature cells that originated elsewhere in the body and
were stimulated to develop into islet cells by signals in the
pancreas. But whatever their origin, the islet cells were working
normally, raising the question of whether the same treatment strategy
would work in humans. That is an ultimate goal, Dr. Nathan said,
while cautioning, “we’re a long way from that.” He estimated it would
take at least a couple of years before the investigators were ready
to try the most preliminary studies in humans. But, he added, he is
excited. “This is really cool,” Dr. Nathan said. “It provides the
possibility that you could take people with Type 1 diabetes or other
autoimmune diseases that are involved in the destruction of tissue
and, if you interrupt the diseases, maybe these cells would regrow.”
The other organ whose cells now appear to regenerate is the heart.
And while some heart disease experts are astonished, the scientist
who led the study, Dr. Piero Anversa, a heart researcher at New York
Medical College in Valhalla, said he never believed the dogma that
the heart did not grow new cells. Last year, his group reported
tantalizing evidence that he was right. Scrutinizing the hearts of
people who had died shortly after having heart attacks, Dr. Anversa
and his colleagues reported that there were dividing cells
in the damaged hearts and that those cells were most numerous in the
heart tissue that was next to the area killed by the heart attack.
Heart disease experts were overwhelmed.
“This is a breakthrough, at least for a new way of thinking about the
heart’s recuperative power and ways to repair a damaged heart,” said
Dr. Valentin Fuster, a former president of the American Heart
Association. But Dr. Anversa wanted to learn where those new heart
cells came from. Are they already in the heart or do they come from
elsewhere, like the bone marrow? Marrow is known to have immature
cells that, in theory, can develop into specialized cells if they are
given the right biochemical signals. He and his colleagues hit upon a
way to find out. They would look at men who had received heart
transplants from women. Male cells have a Y chromosome, and female
cells do not. So if, on autopsy, the female hearts that were
implanted in men contained mature cells with Y chromosomes, that
would be proof that the cells originated outside the heart, coming
from the man’s own cells, possibly from stem cells already present in
his body and ready, when signaled, to become heart cells. Reporting
in the Jan. 3 issue of The New England Journal of Medicine, Dr.
Anversa and his colleagues said there were abundant male cells in the
female hearts. Asked why a healthy transplanted heart would need to
grow new cells, Dr. Anversa said the new heart was not necessarily so
healthy. “The heart is subjected to a tremendous amount of stress,”
he said. Typically, a donated heart is stored for hours before it is
transplanted. And, he said, women tend to have smaller hearts than
men, a fact that could strain the female hearts as they tried to
supply blood to the larger body of a man. The female hearts may need
new cells to replace ones that were injured or died in the process of
transplantation and they may need to grow larger to meet the
new demands on them. Now, Dr. Anversa said, the challenge is to learn
where the cells that colonize the heart come from and how to direct
the process so that the heart can repair itself. Dr. Irving L.
Weissman, a stem cell researcher at Stanford, suggested another
possible way to repair hearts. “If we knew there was a cell outside
the heart that could help regenerate the heart,” he said, “we might
be able to transplant it into the heart.”
But one question looms over the new research: if the body is so good
at growing new cells like heart cells and pancreas cells, why does
anyone develop diabetes or heart disease? Why can’t the body just
constantly regenerate its organs when cells die? The diabetes work
provides an explanation, Dr. Faustman said. If the environment is
wrong in this case, an underlying autoimmune disease causing
diabetes the body’s regenerative mechanisms may be unable to
keep
up. The same thing could happen with damaged hearts, she said.
Patients with heart disease may have such severe damage to their
hearts that the organs may no longer have the scaffolding or the
chemical signals for new cell growth. That observation provides a
warning for research on stem cells, she added. It may not be enough
to provide new cells to patients if nothing is done to change their
underlying disease.
“Even if you clone vats of these cells, if you don’t change the
environment of the host, they won’t do their job,” Dr. Faustman said.
But the work also provides new hope for medicine, researchers said.
In an editorial accompanying Dr. Anversa’s recent paper, two editors
from The New England Journal of Medicine, Dr. Robert S. Schwartz and
Dr. Gregory D. Curfman, noted that the findings had enormous
implications. They “raise the hope that counter to traditional
beliefs, the heart can repair itself,” they wrote. That means, they
said, that scientists may be able to prompt that repair.
They believe that is not such an impossible aim. “Such approaches to
therapy,” they wrote, “which previously were only pipe dreams, are
now realistic goals that may soon be within reach.”
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