Scientists used to think that such potential for cellular
regeneration was present only in embryos -- that, for
example,
humans had made their lifetime supply of brain cells by
age 17.
But that canon is steadily eroding. In the early 1990s,
researchers
isolated human blood stem cells from adults. And earlier
this month,
researchers at Osiris Therapeutics Inc. in Baltimore found
a stem
cell in adult bone marrow that is capable of becoming
bone,
cartilage or fat. Researchers also believe they may be
close to
identifying stem cells in the liver, brain and pancreas.
They're Everywhere
"I think we will find these stem cells in any organ that
we look,"
says Harvard Medical School researcher Evan Y. Snyder, who
has
already isolated brain stem cells from a human fetus and
believes it
won't be long before someone finds them in adult humans.
"I think
that when nature develops a strategy for development and a
strategy
for self-repair, it doesn't make it up each time for every
organ."
Some scientists remain skeptical that stem cells will be
found in
every organ. And hunting is a laborious process. Brain
stem cells
were found in animals a decade ago, but scientists are
still working
to find them in humans. But if and when they are found,
precursor
cells would circumvent the ethical and legal problems of
working
with embryonic stem cells taken from aborted fetuses.
Douglas A. Melton, chairman of the department of molecular
and cell
biology at Harvard University, has found promising results
in mouse
and frog stem cells but hasn't been able to obtain human
embryonic
cells to apply the work to humans.
The National Institutes of Health has said it will permit
federally
funded researchers to use stem cells as long as they don't
actually
handle aborted fetuses, but the cells won't be available
until
formal guidelines for their use have been published.
Meanwhile, work
with the stem cells found in adults is moving along
rapidly.
In early clinical trials in the area of AIDS, Novartis AG
is
purifying blood stem cells from HIV patients' own blood,
altering
them by inserting anti-HIV genes and then reinjecting them
in the
patients. "We expect the modified stem cells will give
rise to
progeny cells that are HIV-resistant," says Carol
Grundfest, a
Novartis spokeswoman.
Cytotherapeutics Inc., of Lincoln, R.I., is looking for
stem cells
in the liver, the pancreas and the brain. It reasons that
a single
type of stem cell may prove useful against many
conditions -- a
brain precursor cell, for example, could be used against
Parkinson's, Alzheimer's and other degenerative brain
diseases.
"The best concept is a drug-in-a-bottle concept -- a cell
product
that is not patient-specific that could be used to treat a
wide
spectrum of diseases," says the company's chief executive,
Richard
Rose.
Developing Substances
Some companies aren't waiting for specific types of
precursor cells
to be discovered. Instead, acting on the belief that such
cells do
exist in certain body areas, they are developing
substances that can
activate them.
One such company is Creative BioMolecules Inc. of
Hopkinton, Mass.
Its drug, osteogenic protein, is now being implanted in
broken legs
that have been slow to heal in clinical trials, and the
company says
results are promising. It believes the drug works by
spurring bone
stem cells to create new bone, says in-house scientist
Marc
Charette.
"The body has a large amount of stem cells, and what you
really need
is the signals to cause them to differentiate," he says.
If the Food and Drug Administration approves the company's
drug, it
will be sold by partner Stryker Corp., of Kalamazoo, Mich.
Biogen is hoping it has found a chemical signal that
causes brain
stem cells to become the type of cells that produce the
neurotransmitter dopamine. Those cells are damaged in
people with
Parkinson's disease, causing its sufferers to have
difficulty moving
and talking. In a collaboration with Ontogeny, Biogen is
injecting
rats with a type of protein known as a "hedgehog," which
has been
shown to play a key role in fetal development.
To simulate Parkinson's disease, the rats are injected
with a toxic
chemical. Normally, the toxin shuts down the animal's fine
motor
control and causes the rat to spin uncontrollably, like a
top. But
the company found that rats given brain injections of the
hedgehog
protein in addition to the toxic injection got a much less
severe
case of the spins, says Joseph M. Davie, the company's
senior vice
president of research
At the very least, says Dr. Davie, the hedgehog protein
appears to
be protecting the brain from the toxin. At best, hedgehog
may
actually direct stem cells in the brain to create new
nerve cells to
replace those destroyed. In a separate project, Ontogeny
is hoping
to generate a therapy that would cause pancreatic tissue
to
regenerate itself, restoring insulin-making capability and
freeing
diabetics from daily injections.
The first step, which the company is now working on, is to
find the
chemical signals -- generally proteins -- that tell a
developing
embryo to make a pancreas in the first place. If they can
be found,
they could be injected into the pancreas in order to spur
stem cells
to turn into insulin-producing cells.
Margaret Tuchman
Princeton, NJ
B1941/Dx1980
[log in to unmask]
