NYT article on spinal cord repair developments.
(Not positive this is relevant to CTII, but interesting (and hopeful) nonetheless ...)
January 25, 2000
Outgrowth of New Field of Tissue Engineering
By HOLCOMB B. NOBLE
Researchers at the University of Massachusetts Medical School have
taken immature cells from the spinal cords of adult rats, induced them
to grow and then implanted them in the gap of the severed spinal
cords of paralyzed rats.
Within two weeks,
the paralyzed animals
began to move, the
scientists say, and
within three months
several of them could
stand and walk.
The experiment is one
of several at
laboratories around
the world that
researchers say
provide increased
evidence that, with
still much more
research to come,
they will be able to
conquer one of the
oldest problems in
medicine: treating
people permanently
paralyzed as a result
of severed, crushed
or diseased spinal
cords.
Dr. Charles A.
Vacanti, who headed
the team at the
University of
Massachusetts in
Worcester, said the
animals could not
scurry like normal
rats but walked in a
coordinated way.
Some lived two years
longer with no loss of
mobility, he said.
"To us this was a
spectacular finding,"
Dr. Vacanti said,
"showing not only
that the animals
recovered their ability
to walk but also to
perceive fairly normal
sensation."
Once the spinal cord is severed, the chances of recovering anything
approaching normal mobility are regarded -- as has been the case for
centuries -- as zero. Over the years, other researchers have reported that they
have recovered such function in animals only to have the reports prove false
or unable to be replicated.
The reaction to the University of Massachusetts work among medical
scientists has been varied. Some call it a stunning accomplishment; others
want to wait for further research, with one suggesting that the new mobility
may simply be "step walking," a kind of jolting, muscle response that may
come from the experimentation itself rather than from brain messages.
Still the Massachusetts work is one of the most startling efforts in the rapidly
evolving field of tissue engineering in which biologists and biomedical
engineers are growing living tissue in incubators and bio-reactors. The goal is
to create living replacement parts for the human body that will work better
than synthetic parts or scarce transplants.
Dr. Vacanti's team has been working in collaboration with a team headed by
his brother, Dr. Joseph P. Vacanti at Harvard Medical School -- in fact, a
total of four Vacanti brothers are involved in tissue engineering -- and a team
headed by Dr. Robert Langer at Massachusetts Institute of Technology.
The Harvard and M.I.T. groups recently collaborated in growing a small,
partially functioning liver that was able to produce albumen, one of many
proteins that contain essential building blocks of the body.
They and others, at Laval University in Quebec, Duke University in Durham,
N.C., and elsewhere, have grown live blood vessels from human cells and
animal cells and tested them in animals with initial success. And peripheral
nerves are being produced that repair animal nerve damage to degrees that far
surpass the standard treatments.
In all, university and private scientific labs are at various stages of growing
some 23 forms of live tissue, including live cartilage to repair muscle
structure without surgery and skin grown from human cells.
Dr. Joseph Vacanti is now working toward the goal many would regard as
the piŠce de r‚sistance of tissue engineering: growing a human heart.
In a recent interview at the Massachusetts General lab, he held up an elegant
model of a sheep's heart, with the graceful line and symmetry of sculpture. It
was built by a plastics manufacturer to specifications supplied by Harvard
and M.I.T.
"Basically, we pumped a liquid plastic into the blood supply of a sheep's
heart," he said. "When it hardened, we removed the animal tissue chemically,
and have the mold of the sheep's heart."
Dr. Langer's lab is now electronically scanning slices of the mold so a
computer can make a three-dimensional reconstruction and a mathematical
model.
With this, a new mold of biodegradable plastic will be made. That will be
seeded with heart-tissue cells that are to regenerate as the plastic disappears.
The hope is that eventually that such cells can be made to grow into a beating
implantable sheep's heart.
Much of this delicate and sophisticated tissue engineering grew, in a sense,
out of seaweed on a beach on Cape Cod in 1986.
Dr. Langer and Dr. Joseph Vacanti had been pondering how to create
polymer, or plastic, molds that were thick, strong and durable enough to last
and yet delicate enough to perform intricate tasks, like delivering blood
through the tiniest of capillaries. While he walked on the beach Joseph
Vacanti spotted a piece of seaweed with a tough exterior and finely detailed
interior branches. He ran to a telephone and called Dr. Langer: "Could we
design polymers that had a branching structure like that?"
"Well," came the reply, "we could probably do that." They did, and molds
with tough exteriors and interior branches and channels are now in
widespread use in the science of growing living tissue.
The new University of Massachusetts spinal-cord work by Dr. Charles
Vacanti has been reported at a medical meeting in London of the British
Tissue and Cell Engineering Society and widely discussed among biomedical
engineers and neurologists at other medical meetings.
He declined to reveal the detailed data of the study while an article about it is
under peer review for a medical journal.
But he described the work in general terms: The team took spinal-cord cells,
from adults animals, that had matured to the progenitor stage -- developed, or
differentiated, enough to belong generally to the spinal cord but not enough to
be assigned to any specific part of the cord.
Then, in a petri dish inside an incubator with the right nutrients, heat and
oxygen supply, the cells regenerated into a large enough population to begin
tissue growth. But they were not allowed at this stage to differentiate further.
The spinal cord is thought by some to be made up of separate fibers, like
wires in a telephone cable, which, if severed, must be reconnected precisely,
red wire in one section, say, with the red in the other. But Charles Vacanti's
group believed this connection might not have to be made directly but could
come about on its own.
The team put its not-fully differentiated progenitor cells in a four-millimeter
break in the rats' spinal cord. There, Dr. Vacanti said, they regenerated into a
new functional section.
Dr. Vacanti said he believed the key was using only progenitor cells, an idea
conceived by another of his brothers, Dr. Martin P. Vacanti, a member of the
University of Massachusetts team.
"The thought was that the undifferentiated progenitor cells, if left on their
own," Martin Vacanti said, "would sort themselves into the right order, and
produce all the necessary functions." This approach is a sharply different
from one being tried by the fourth brother, Dr.
Francis X. Vacanti, a member of Joseph Vacanti's team.
He is trying to implant new spinal cord cells that directly link each nerve fiber
of the new with the matching fiber of the old, in effect connecting "red" line
to "red."
Among other scientists, the responses have been mixed. Assessing the
University of Massachusetts work, Dr. David J. Mooney, a biomedical
engineer at the University of Michigan, said, "What Charles Vacanti and his
team have accomplished is simply stunning."
Dr. Henry Brem, a professor of neurosurgery at Johns Hopkins University,
said he would be trying the techniques in his own research.
Dr. Joy Young, professor of cell biology and neuroscience at Rutgers, said
that with similar work elsewhere, the recent efforts carry strong promise for
improving the outlook for patients with spinal-cord damage, now estimated to
be 300,000 to 500,000 people in the United States. Work at Washington
University in St. Louis and at the University of Florida, among others, has
involved fetal and embryonic cells that have been transplanted into animal
spinal cords and appear to have taken hold.
Other neurologists were more cautious, among them, Dr. Evan Snyder at
Harvard Medical School and Children's Hospital in Boston, one of the first to
isolate the most primitive cells of the brain.
He and others recognized that contrary to what had long been believed,
undeveloped brain cells in adults could be developed, with the potential for
treatment of a wide variety of diseases, for conditions as diverse as heart
failure and Lou Gehrig's disease.
Another year may be needed, Dr. Snyder said, before "we can really prove
that severed spinal cords can be repaired, with reconnections really made,
allowing the brain-message delivery that permits mammals to regain normal
mobility."
He agreed that what the University of Massachusetts team had done was
interesting but said it was possible that its experiment might have produced a
kind of local "step walking" ability that stemmed from muscles, not brain
signals, as seen in previous experiments with cats, for example. But Dr.
Charles Vacanti said observers found that the walking appeared to be
coordinated rather than the jerky style seen in step-walking. The animals also
recovered sensory function, he said, as well as developing new tissue, all
signs that led the team to conclude that real connections between the new
spinal cord and the old had been made.
Whether Dr. Snyder himself or one of the Vacanti teams are closest to the
mark, they all find themselves in a highly competitive area of research.
It is not uncommon for researchers trying to achieve the same results to be
secretive about the work and progress. But the four Vacanti brothers do not
seem to fit that pattern.
"We actually talk to each other all the time about what we're doing," Charles
Vacanti said. "Otherwise we never could have progressed as well as we
have."
Copyright 2000 The New York Times Company |
