Story originally printed in the La Crosse Tribune or online at www.lacrossetribune.com
Published - Monday, September 25, 2006
Many fields see great potential in stem-cell research
MADISON — Gabriela Cezar is a stem-cell researcher at UW-Madison, but she’s not studying the cells as potential cures.
She’s trying to come up with tests to detect disorders such as autism.
In her lab, Cezar exposes dishes of embryonic stem cells to the epilepsy drug valproate. Studies have shown that the drug, when taken by pregnant women, increases babies’ risk of autism, spina bifida and skeletal deformity.
The cells release biological signals in response to the drug. Cezar wants to test children with autism and related conditions to see if their blood harbors the same signals. If so, the signals might be detected in a blood test on fetuses or babies.
“We want to be able to diagnose these diseases earlier” so patients and families get help quicker, she said.
Cezar’s work illustrates the wide scope of research by the university’s more than 110 stem-cell scientists.
And Czar herself illustrates the university’s prominence in the field, which started when researcher James Thomson grew the world’s first stem cells in a lab in 1998.
The university lured Czar, 34, last year from the drug company Pfizer, largely because of the high profile of researchers here.
But she and other campus scientists say Madison’s reputation in the field could be in jeopardy if Republican gubernatorial candidate Mark Green defeats Democratic Gov. Jim Doyle in November.
Green, a U.S. representative from Green Bay, says he supports stem-cell research. He has called for $25 million in state funding on an experimental method of obtaining the cells without destroying embryos, as the current method does.
But Green wants to maintain funding restrictions on the current method and institute a ban on so-called therapeutic cloning. Doyle opposes both moves.
Such restrictions could drive scientists away from the state, Czar and others say.
“We have the best people in the world here,” she said. “Wisconsin should do whatever it can to keep this talent here.”
Thomson, who has become the de-facto quarterback of the university’s stem-cell research team, is quick to say he wants to stay out of politics.
But when it comes to the governor’s race, Thomson is concerned about perception, he said. California, Connecticut and New Jersey are among a growing number of states directly investing in stem-cell research.
Wisconsin, despite spending $50 million for a research complex at UW-Madison that will involve stem cells, is not directly supporting the research.
“If they go beyond that and make it sound restrictive here,” Thomson said, “it’s going to be really hard to recruit people to the state.”
Embryonic stem cells are master cells, considered capable of becoming all of the body’s 220 cell types, from blood to bone to brain. Growing them currently requires the destruction of five-day-old embryos. The new, experimental technique aims to get around this ethical hurdle.
Since Thomson’s discovery transformed biology and launched a new national debate about the beginning of life, scientists on campus have been gradually growing embryonic stem cells into a variety of cell types.
The cells, they say, could lead to therapies that replace or repair diseased or damaged tissue in people with Parkinson’s disease, heart disease, diabetes, spinal-cord injury and other conditions.
The trick is figuring out which materials should be added to lab dishes to direct the cells into a specific type — such as brain cells that produce the chemical dopamine, which people with Parkinson’s lack.
Scientists also have to make sure the cells, if transplanted into patients, don’t turn into something else, such as a tumor. And they must overcome immune-system rejection of the cells.
For now, scientists using federal money — the mainstay of biomedical research — must rely on 21 clusters, or lines, of stem cells approved by the Bush administration. The cells were created before August 2001.
But because those cells, including five lines created by Thomson, were grown with animal products, it’s unlikely they would be considered safe enough for studies in humans.
Thomson and his colleagues recently used private money to derive two new stem-cell lines, the first in the world known to contain no animal products.
For stem-cell research to ever reach the clinic, many more such lines must be developed and studied, said Carl Gulbrandsen, managing director of the Wisconsin Alumni Research Foundation, which holds three patents on Thomson’s cells.
Gulbrandsen is worried about Green not only because Green opposes federal funding to create new stem-cell lines using existing methods, but also because Green could seek to ban the creation or use of new lines in the state, even those made with private funds.
“It’s absolutely essential for us to have access to newly derived lines,” Gulbrandsen said. “I would hate to see any attempt made to prevent us from doing that.”
Mark Graul, Green’s campaign manager, denied that’s part of the plan.
“There is nothing on the books today preventing private companies from conducting embryonic stem-cell experiments,” Graul said. “That’s not going to change under a Gov. Green.”
Given the hurdles, progress in stem-cell research at UW-Madison is slow. But possibilities continue to unfold.
Blood cells: Igor Slukvin, who studies blood, said he can coax embryonic stem cells to become nine of the 10 types of blood cells. The cells could be grown into red blood cells that are O-negative, the universal donor type, so blood could be transfused in emergency rooms or on battlefields without having to check for compatibility, he said.
“Young” red blood cells could be created to allow transfusions to last longer, reducing the frequency of the treatments in patients with anemia, he said.
Slukvin can also grow embryonic stem cells into dendritic cells, immune-system cells used in experimental cancer vaccines.
Slukvin’s line of research is among the most controversial because some types of blood cells already can be produced with “adult” stem cells, which can be harvested without destroying embryos.
Green and many religious conservatives prefer research on adult stem cells.
But Slukvin said embryonic stem cells are more promising for his studies for a simple reason: They can be easily grown in lab dishes. Adult stem cells can’t.
“You just can’t get enough of them,” he said.
Heart cells: Tim Kamp, who is growing embryonic stem cells into heart cells, wants to use them to repair heart attacks.
In a study he conducted last year in mice, stem cells from mouse embryos were injected into the hearts of mice after surgeons induced heart attacks. The cells formed three types of heart cells and partially restored heart function, Kamp said.
Similar studies in humans remain years away. But in the lab, Kamp has grown human embryonic stem cells into three major types of heart cells, some of which beat like tiny hearts in his petri dishes.
He is studying the cells’ electrical and mechanical properties, with the hope of learning how gene mutations affect heart function.
“They’re basically a very powerful research tool,” Kamp said.
Other UW-Madison scientists agree that the discoveries they are making about how cells become organs and how organs become diseased could be as important as any potential therapies involving replacement cells.
Until human embryonic stem cells became available, scientists had to rely on worms, mice and zebra fish for such knowledge.
“If never a therapy is developed from human embryonic stem cells, which I doubt, there is still a huge benefit in using these cells for understanding basic human development,” said Dr. Jon Odorico, a UW Hospital transplant surgeon.
Pancreas cells: Odorico is working on what may be stem-cell science’s most widely-discussed goal — creating pancreas cells that produce insulin to treat diabetes.
Like other surgeons around the country, he has already transplanted such cells, called islets, from deceased donors into diabetics. Some patients have been able to give up insulin shots.
But the supply of donor pancreases is limited, Odorico said. Islets grown from embryonic stem cells could enable many more transplants.
For now, he is trying to produce pure populations of islets from the embryonic cells.
Brain cells: Su-Chun Zhang’s research focuses on brain cells that could help people with Parkinson’s, Lou Gehrig’s disease, multiple sclerosis and other neurological conditions.
He has grown embryonic stem cells into motor neurons, spinal-cord cells that control movement. He has also created neurons that produce dopamine, which could help people with Parkinson’s.
Zhang has started transplanting the cells into mice with spinal-cord injury and Parkinson’s. It’s too early for results, he said.
Like the other scientists, Zhang fears Green might try to limit stem-cell research in Wisconsin. He’s also perplexed that some people consider what he does unethical.
“It would be a shame to stop or slow down this research here, a leading place in the world,” he said.
“We are scientists,” Zhang said. “We aren’t doing anything like killing people. We want to help patients.”
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