Strokes are responsible for more than one
out of every 15 deaths in the United States, according to a 2004
American Heart Association report. For every death, there are many
more survivors who must cope with symptoms ranging from paralysis
to speechlessness. Rehabilitation options are limited and often
involve a process of physical therapy that is grueling for both
patient and caregiver. Even then, results are modest and little can
be done to treat the damage done to the brain by the stroke.

Neurology Prof. Jack Parent is trying to develop a method to
treat this stroke-related brain damage directly by using stem cells
— self-renewing cells that can give rise to all other kinds
of cells in the tissue in which they are present.

Parent is studying the ability of brain cells to self-repair
after a stroke. After finding that the self-repair scenario was
less promising as expected, he realized that another strategy was
necessary and looked to stem cells as an alternative.
Theoretically, stem cells could be implanted into the brain and
grow into new nerve cells to replace the ones damaged by a stroke,
he said.

Stem cells are “a potentially unlimited source of new
nerve cells for the brain,” Parent said.

But before stem cells can have any therapeutic value, more
research is needed to understand why they differentiate into
different types of cells and how to use them to produce desired
cells in humans, Parent said.

Making this research possible is a grant from the
University’s year-old Human Embryonic Stem cell center. In
September of 2003, the University received a three-year, $2.3
million grant from the National Institutes of Health to establish a
human embryonic stem cell center—one of three in the nation.
The center awards three grants of $75,000 to scientists pursuing
embryonic stem cell research each year. The researchers also
receive access to three federally approved stem cell lines.

In its first year, the center has been focused on getting stem
cell lines to the University and establishing a proper environment
for research, said K. Sue O’Shea, a professor of cellular and
developmental biology and head of the center.

“For the first year we were funded, we spent a lot of time
getting stem cells in-house and establishing (research) protocols.
We’ve got to be very careful so that we don’t change
them in any way,” O’Shea said.

Now that the center has received and produced copies of its cell
lines, its researchers are producing valuable data, said
O’Shea.

“(The researchers) are coming along. They all have some
good things that are happening and it’s enough info to see if
it’s worth it to pursue it as a line of work.”

By providing funding and access to stem cells, the center will
serve as a stepping stone for scientists to receive their own NIH
grants, O’Shea said.

 

Beyond the science

Mentioned by both Democratic presidential candidate John Kerry
and his running mate John Edwards on the campaign trail, embryonic
stem cell research has become a key polarizing issue in an already
heated political season. Candidates have traded blows over stem
cells while party loyalties have been tested; While President Bush
has come out against embryonic stem cell research, California Gov.
Arnold Schwarzenegger, a Republican, came out in support of
spending $3 billion of public funds on research.

This initiative dwarfs the $25 million in federal funds
President Bush has provided for stem cell research and the $100
million a year proposed by Kerry. But the major difference between
Bush’s and Kerry’s plans — the difference that
has become politically important — is that President Bush
restricted embryonic stem cell research in 2001 to the 78 lines
then in existence, while Kerry supports unrestricted research on
unlimited lines.

Supporters of embryonic stem cell research argue that more lines
need to be developed and opened in order to unlock the true
potential of stem cells, while others question the morality of
destroying embryos to obtain the cells.

Working on the front lines of embryonic stem cell research,
O’Shea is quick to weigh in on the issue. The so-called
“presidential stem cell lines” are inadequate for
research because they are not pure enough to be used in humans, she
said.

“All the cells President Bush restricted us to use were
derived in contact with mouse embryo fibroblasts — that means
they may have mouse viruses in them … It is very unlikely
that the FDA will allow the early presidential cell lines to be
transplanted into other humans,” O’Shea said. The more
recently derived lines were not in contact with mouse embryos and
therefore are not contaminated.

More cell lines also means more genetic variability.
O’Shea said that by developing lines from embryos of families
with different genetic diseases, scientists could develop a greater
understanding of the afflictions and come up with possible
remedies, something that current restrictions are hindering.

O’Shea said the state of Michigan has not been as
supportive of stem cells as it could be and is being overshadowed
by states that recognize the importance of stem cell research.

“(Legislators) haven’t encouraged us in any way
while California has been throwing a lot at (stem cell research)
— they see the power of stem cells and the ability to
increase growth and economic development.”

Rep. Jack Hoogendyk (R-Kalamazoo) is one legislator trying to
limit the scope of stem cell research in Michigan. Last April,
Hoogendyk introduced a bill aimed at banning research on embryonic
stem cell lines not derived from the presidential lines. Although
the destruction of embryos, and therefore the derivation of new
stem cell lines, is currently prohibited in Michigan, Hoogendyk is
concerned that researchers could import lines made outside the
state.

“(I believe) that all human life is guaranteed protection
by the Constitution; the size of the human life has no bearing on
this protection,” Hoogendyk said. “The first question
is, ‘Is it a living human?’ ”

Embryonic stem cell research does not warrant the destruction of
an embryo, Hoogendyk said.

By using adult stem cells, researchers have been able to
accomplish major breakthroughs without the destruction of embryos,
Hoogendyk said.

“To date, there has been no progress with embryonic cells.
The only breakthroughs that have occurred — and there have
been some significant ones — have been with adult stem cells,
that is, stem cells taken from humans who have already been
born,” Hoogendyk said.

Though tabled, Hoogendyk’s bill may be picked up for
consideration in the next legislative session.

 

To the future

Work continues at the center even as the fate of human embryonic
stem cell research in the United States is being decided on the
political battlefield.

Parent continues trying to determine whether stem cell
transplantation is possible in the brain.

Getting stem cells to grow into nerve cells isn’t the main
problem; their natural tendency is to develop into the cells,
Parent said. Rather, he is trying to find out at what period in a
stem cell’s development it is most receptive to
transplantation. If stem cells are too mature when implanted into
the brain, they will not migrate to the site of the stroke damage.
However, if they are too immature, they won’t become nerve
cells.

To examine the behavior of stem cells after transplantation,
Parent and his colleagues are also developing a way to track stem
cells noninvasively. This involves radioactively tagging the stem
cells and following them with a PET scan, similar to the procedure
used when tracing a person’s blood flow.

This fall, three more projects were selected to receive funding
from the center.

Mark Russell, a professor of pediatric cardiology, heads one of
these projects. He is interested in the differentiation of
embryonic stem cells into beating heart cells.

“We would like to understand how cells make the decision
to become cardiac muscle cells: What cues are they using from the
surrounding tissue to drive them to become cardiac muscle
cells?” Russell said.

Russell hopes to gain insight into the signaling process that
generates heart muscles in order to pave the way for a way to
repair muscle damaged by heart attacks.

Only about a month into his research, Russell is nonetheless
excited about the potential of the center.

“It’s a very important effort and it’s
terrific that we can attract this center to Michigan. I think this
will make Michigan a leader in the field for many years to
come.”

With the support offered by the University, which gave $500,000
to help with start-up costs, O’Shea sees the center as a
permanent part of the University research community.

She hopes the center will expand its scope and use embryonic
stem cells to make models of diseases and, depending on changes in
embryonic stem cell policy, to study a variety of genetic diseases
using newly derived stem cell lines.

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