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Around the
world, adult stem cells are being used in experimental procedures to heal
hearts, regenerate bones and grow human tissue.
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When Amit
Patel says he operates in three different time zones, he's not just
complaining about his constant jet lag. Patel, a heart surgeon, is based
at the University of Pittsburgh. But in the last four years, he's done his
most exciting experimental work in South America, cracking his patients'
chests, looking for blockages in their vessels--and then, if he can't
clear the obstructions, injecting the patients' hearts with stem cells
drawn and cultured from their own bone marrow.
Patel has been
deluged by hopeful heart-failure sufferers. Since he can't see them all,
he refers some of them to Bangkok. Surgeons can perform a similar
procedure
there, but they lack the facilities to culture stem cells. So those
patients' cells are sent on a global odyssey: harvested in Thailand,
loaded onto a daily El Al flight, cultured in Israel, returned to Bangkok
and finally shot back into the body from which they were derived.
Literally and metaphorically, those stem cells have come a long way.
<P
While U.S.
politicians have been bickering over embryonic-stem-cell research, doctors
around the world have been staging a quiet revolution--regenerating jaws,
restoring corneas, building bones, heartening heart patients--and they've
completely circumvented the embryonic conundrum. Their secret weapon?
Autologous stem cells, which come not from days-old human embryos but from
the anatomical nooks and crannies (particularly the bone marrow and blood)
of adults. Embryonic stem cells may be the most versatile in the lab, but
they have yet to be tested in a single human being. Their autologous
counterparts have the promise of transforming patients' lives now. While
most of the breakthroughs so far have been realized outside U.S. borders,
at least a few people think that's about to change. Patel is one of them.
Another is Charles Vacanti, the chair of anesthesiology at Brigham and
Women's Hospital in Boston. "In this country we aren't moving very rapidly
from the lab into people," he says. "But it's time."
<P
That may
simply sound like the pronouncement of an optimist, but then organ
regeneration via stem cells is the Vacanti family business. Several years
ago, Charles Vacanti built a new thumb for a patient out of sea coral and
the patient's own bone-marrow cells. His brother Joseph, a surgeon at
Massachusetts General Hospital, is also a pioneering "tissue engineer."
Joseph has grown skin replacement for burn victims and heart valves in
sheep. Now the Vacanti brothers are preparing for an upcoming
bone-replacement trial. The study is still taking shape. In one version of
the trial, the doctors will work with back patients who have had their
intervertebral discs removed. Rather than implant titanium spacers where
the discs usually reside, the Vacantis are hoping to use the patients' own
stem cells to grow bone tissue there. Alternately, they may expand their
study to the rest of the body. One of Charles Vacanti's young students is
a recovering cancer patient; a bone in her leg had to be removed and
replaced with one from a cadaver. The bones of the dead are useful for
trans-plant purposes, but they often have weak spots that can cause
breakage after implantation. Instead, says Charles, if autologous stem
cells work in bones, surgeons may be able to remove only the cancerous
part of a patient's original bone, and then grow it right back.
<P
The
Vacantis will have an army's worth of American doctors eagerly awaiting
their results. Already, scientists are working on a variety of other
autologous stem-cell therapies. Genzyme, the biotech firm, has been making
replacement cartilage from autologous stem cells for the last 10 years and
recently introduced a new version that allows for faster and cleaner
implantation. Doctors at many top cancer centers are using autologous stem
cells as an experimental treatment for leukemias, Hodgkin's disease,
malignant lymphomas, multiple myeloma and breast, ovarian and testicular
tumors when conventional therapies fail. And while it could take as long
as a century before doctors can use stem cells to regenerate large,
complex organs like the liver, scientists are actively trying to grow
human tissues in the lab. Their experiments may someday allow doctors to
restore movement to paralyzed stroke victims or regenerate parts of the
brain.
<P
Even now,
researchers outside the United States are accomplishing similar
feats--sometimes so far out as to resemble science fiction--in humans.
Last August, German doctors announced that they had regenerated the lower
jaw of a patient who had lacked one for nine years because of a cancer
resection. Researchers created a mandible out of titanium mesh and the
patient's bone-marrow stem cells, implanted the structure in the patient's
back muscle, "grew" it there for seven weeks and then took it out and
attached it to the upper jaw. The operation was a success. The patient,
who had eaten little more than soup for the last decade, promptly
celebrated with a chewy bratwurst sandwich.
<P
A month
later, doctors in Osaka reported that they had coaxed stem cells from four
patients' mouths into something else entirely--eye cells that were used to
regenerate the fragile outer layers of the patients' corneas. (Mature eye
and mouth cells both start out as the same type of epithelial stem cell.)
A year after the operation, doctors say the patients seemed to be doing
well, with the new corneal cells appearing to be in perfect working order.
<P
Americans
with poor eyesight shouldn't start running off to Osaka just yet, though.
It's far too early to assume that this radical procedure will ever become
standard practice. Many U.S. doctors reacted with skepticism to the
Japanese announcement. Some ophthalmologists noted that cultured
epithelial cells tend to deteriorate after a few years. Others said they
needed to see more evidence, and most probably won't truly believe the
results until they've been replicated here at home. The Japanese have
shown great enthusiasm for stem-cell research--maybe, some doctors hinted,
they were getting a little ahead of themselves.
<P
Of course,
U.S. doctors want to keep up with their counterparts. But, as with so much
cutting-edge research, homegrown-organ techniques tend to run into two
hurdles in this country: the FDA and funding. Even though autologous
stem-cell therapies don't carry the same rejection risks as traditional
transplants, the FDA oversees them with the same kind of vigor because the
cells are cultured outside the body in an incubator. Doctors also often
find that once they've submitted a plan for an experimental operation,
it's nearly impossible to tweak it without going through the approval
process again--even if the change is likely to benefit the patient. Then
there's the issue of money. Autologous stem cells are more difficult to
obtain in large quantities than embryonic stem cells and also shorter
lived. Processing them is costly, and very few companies specialize in it.
Allogenic stem cells, which come not from the patient's body but from
other adult donors, "are less expensive," says Vacanti. There's just one
little problem, he adds: "Frankly, they don't work."
<P
If doctors
can overcome those two obstacles, the coming decade will likely see a
flowering of new therapies using autologous stem cells. Patel, for his
part, has recently obtained clearance from the FDA to start performing his
heart operation in the States. Perhaps that's because his preliminary
results thus far have been so tantalizing. Nearly all the patients from
his South American trials who received their own stem cells--patients who
were "truly at the end of all standard therapy" for blockages, myocarditis
or congestive heart failure--have improved dramatically, with almost no
side effects, he says. According to his experimental design, Patel gave
only half the patients stem cells. The others received their own serum as
a placebo. But Patel also gave the latter group the option to come back
and go under the knife again, this time with stem cells included. Nearly
all of them have accepted the offer.
<P
That's
quite a leap of faith, considering that no one really knows why stem cells
seem to work. The injected cells may be fusing with nonworking cells in
the heart, forming new blood vessels and heart muscle or acting as "homing
signals," bringing curative growth factors to the site of trauma. Whatever
the truth might be, Patel is hoping to get closer to it in the next few
years. In May, he finally operated on a patient in his hometown of
Pittsburgh. The patient is also awaiting a heart transplant. When a donor
organ becomes available and the heart that Patel treated is removed, he
will be able to study his handiwork. After he's performed the operation on
an additional five to 10 transplant patients, and retrieved their old
hearts, he thinks he'll be able to figure out what those injected stem
cells have been up to. Once he does, Patel may finally be able to get some
rest.
<P
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