Embryonic Cells Hold Greatest Promise, Most Researchers Say
By Tina Hesman Of the St. Louis Post-Dispatch

08/22/2004

A group of unassuming cells growing in laboratory culture dishes is now caught in
the glare of a political spotlight: stem cells.

For some the cells hold promise for curing previously hopeless diseases. For
others, they are moral and ethical landmines threatening to destroy the boundaries
between right and wrong.

Stem cells come from a few important sources. The most controversial are
embryonic stem cells, primordial cells formed soon after fertilization that may grow
into any type of cell in the human body. Supporters of embryonic stem cell research
say the cells can cure spinal cord injuries, diabetes, Lou Gherig's disease,
Parkinson's disease, Alzheimer's disease and many other ailments. But research on
human embryonic stem cells is so new that it hasn't led to any treatment yet.

Other people object to the research because the cells come from human embryos,
and they believe that harvesting the cells destroys a human life.

Three years ago, President Bush decided to allow scientists in the United States to
work with embryonic stem cells that already had been harvested up to that time. He
said the government would not pay to make more stem cell lines and would not
support research on stem cells made after August 9, 2001. That decision allowed
scientists to start studying the cells, but ultimately could stifle some of the most
important advances in medicine, scientists say.

The debate over embryonic stem cells has been muddied further by the issue of
therapeutic cloning (see glossary and graphics for an explanation). That technique
could provide replacement parts that would not be rejected by a patient's immune
system, supporters say.

Opponents of embryo work say there is already a good source of cells that the
immune system won't reject: Adult stem cells extracted from a patient's own body.
Most often these cells come from bone marrow, blood or fat (see graphic).

But scientists who study both adult and embryonic stem cells say the adult cells lack
the flexibility of their more primitive counterparts. The road forks early for stem cells,
and no one has figured out yet how to bring an adult stem cell back down its
predetermined path and make it take the road not traveled.

Some early reports that adult blood-forming stem cells (also called by their Greek
name, hematopoietic stem cells) could make nerve cells or pancreas cells have
been disproven. Some scientists still stand behind those claims, but many stem cell
researchers say they no longer believe the data.

"It's safe to say that it's still very controversial," said Jan Nolta, a cell biologist at
Washington University who works with adult stem cells.

Nolta extracts a type of adult stem cell called a mesenchymal stem cell from fat left
over after liposuction or gastric bypass surgeries. These mesenchymal cells, also
called bone marrow stromal cells, act as internal paramedics. They are the first on
the scene of an injury, where they build a scaffold and call in other stem cells to
repair the wound. Mesenchymal stem cells also can form bone, cartilage, skeletal
muscle and tendons. Clinical trials are under way to use mesenchymal cells to heal
injuries to those tissues, she said.

Nolta and others thought mesenchymal and blood stem cells also might be able to
make liver and heart cells because they seemed to integrate into those organs after
an injury. That would mean that cells could switch programming. The researchers
have since learned that the adult stem cells don't become heart or liver cells.
Instead they fuse with those cells, she said.

The fusion may provide some benefits to patients, Nolta said. But the cells probably
will not be able to replace severely damaged, dying or dead cells in most internal
organs, she said.

Nolta doesn't study embryonic stem cells but says they have some advantages over
adult cells. Scientists must continually replenish stocks of adult stem cells.

Hematopoietic stem cells can't be kept in their primitive state in the lab, she said. As
soon as they are placed in petri dishes, they start forming blood cells. Mesenchymal
stem cells grow happily as unspecialized cells, but only for about 10 rounds of
growth.

"After that, they're kaput," Nolta said.

The cells lose their ability to home in on and repair wounded tissues, she said.

But embryonic stem cells can provide an almost unlimited supply of cells for
transplant, scientists say.

"It's like the famous story of the wine that never ends or the bread that never ends.
You can just start with one cell and you can make billions of cells," said Dr. Lorenz
Studer, a stem cell researcher at the Sloan-Kettering Institute in New York.

And scientists have coaxed embryonic stem cells to do things adult cells can't.

Researchers led by Andre Terzic at the Mayo Clinic in Rochester, Minn., reported
last week in the American Journal of Physiology that they used embryonic stem
cells from mice to heal rats after a heart attack.

Previous attempts in France and Germany to use stem cells taken from a patient's
own muscle or blood failed to make functioning heart cells, Terzic said. Those adult
stem cells homed in on damaged heart tissue and latched on, but never got the
rhythm the rest of the heart ticked to, he said.

"It's like the symphony," he said. "When you have one of the instruments playing off
tune, you have problems."

Some of the patients in the study did improve after the therapy, but scientists say
that it wasn't because the stem cells formed new heart muscles. Rather, the cells
may have recruited new blood vessels to the injured area and helped speed the
healing.

The embryonic cells did not just latch onto the wounded heart the way adult stem
cells do, Terzic said. They actually became heart muscle cells that beat in time with
the rest of the organ, he said.

Studer and his colleagues report in the Aug. 24 edition of the Proceedings of the
National Academy of Sciences that they persuaded human embryonic stem cells to
make dopamine-producing neurons. Those are the brain cells that die in the brains
of Parkinson's disease patients. Studer has cured mice with a similar brain defect
using mouse embryonic stem cells and stem cells cloned from one of the mouse's
own tail cells.

Studer has worked with all kinds of cells - fetal tissue, adult stem cells, and
embryonic stem cells - looking for replacements for the dying dopamine neurons.
Fetal tissue is controversial and required too much material to make it feasible, he
said. Adult stem cells just don't have the versatility needed to change course and
become a brain cell.

"It's not for lack of trying. I spent four or five years trying to develop adult stem cells
(into dopamine-producing neurons) without success," Studer said.

Only embryonic stem cells easily turned into the brain cells Studer was looking for.

"I work with all the cell sources. I don't have any pre-conceived bias, but it's just
simply the fact that (embryonic stem cells) really are the most powerful source," he
said.

Both Terzic and Studer caution that they are still years away from being able to test
their therapies in clinical trials. More animal research is needed, they say.

"The promise is high"

The real barrier to moving embryonic stem cell therapies into the clinic is that the
lines of cells President Bush approved in 2001 are not safe for use in people,
scientists say. Those cells were all grown in contact with animal cells and products -
so-called "feeder cells" from mice that nourish the stem cells, and blood products
from cattle. The Food and Drug Administration is concerned that the animal cells
could pass harmful viruses or other disease-causing agents to the stem cells.

Scientists in Korea, Singapore and elsewhere have made new embryonic stem cells
that never came into contact with animal matter. But those stem cells were made
after Bush's deadline and American researchers can not use federal funds issued
by the National Institutes of Health to study them. Many scientists, patient advocacy
groups, politicians and others say that stem cell research can never live up to its
promise if the funding restriction is not lifted.

"The question is, at the end, whether it a smart strategy to use the NIH approved
lines where we know this risk clearly exists or should we be allowed to use cell lines
that were, from the beginning, derived under conditions that would be suitable for
clinical use," Studer said.

Therapeutic cloning also may allow researchers to create cells free from animal
contaminants. A Korean group announced in February that they had made stem
cells from cloned human embryos, but other researchers have yet to repeat the feat.

Understanding how egg cells reset genetic programming during cloning might help
researchers learn how to make adult stem cells as tractable as embryonic stem
cells, Studer said.

Some researchers have proposed making a bank of embryonic stem cell lines from
which doctors could choose genetically compatible transplant cells for their patients.
But such a bank would include stem cells made after the deadline and would not be
eligible for federal funding in the United States under the current restrictions. The
United Kingdom has already proposed such a stem cell bank.

Even if stem cells fail to live up to their clinical promise, they are invaluable
resources for scientists, said Dr. John W. McDonald, a spinal cord injury researcher
at Washington University. Only 10 percent of stem cells' significance is therapy,
McDonald said. Scientific discovery will account for the majority of the cells'
importance.

"This is not potential. This is predictable," McDonald said.

Stem cells with genetic defects such as ones common in Huntington's disease or
Alzheimer's disease could teach scientists how the defects alter brain development,
he said. Pharmaceutical companies could grow cells with such genetic defects for
drug testing, or screen drugs for toxic effects using liver cells made from stem cells,
he suggested. Those applications are already possible with some newly-created
stem cell lines, but researchers here can only study those cells with private funds.

Proponents of adult stem cell research say they can learn from embryonic stem
cells. Dr. Michael H. Creer, director of the St. Louis Cord Blood Bank at Cardinal
Glennon Children's Hospital, searches for stem cells in blood extracted from
umbilical cords. Cord blood is a source of adult stem cells.

Cord blood cells are more flexible than stem cells taken from mature tissues. But no
evidence yet exists to indicate cord blood cells are as versatile as embryonic cells,
Creer said. But if such a cell lurks in umbilical cords, scientists must first learn how
to find it, he said. That can only be accomplished by learning more about embryonic
stem cells, he said.

Scientists dare not give up on embryonic stem cell research, said David Gottlieb, a
stem cell researcher who grows mini nervous systems from mouse stem cells in his
laboratory at Washington University. His work could teach researchers how the
brain develops. That knowledge could help cure brain diseases. But Gottlieb says
fundamental research on stem cells could lead to unexpected applications that
could change medicine and the world in ways people have never imagined.

"The index of promise is very, very high," Gottlieb said. "When you have something
promising, your only choice is to pursue."

Reporter Tina Hesman writes about science for the Post-Dispatch.

Reporter Tina Hesman
E-mail: [log in to unmask]
Phone: 314-340-8325

SOURCE: The St. Louis Post-Dispatch, MO
http://tinyurl.com/3svh9

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