- The Washington Times - Sunday, January 9, 2005

It’s easy to forget that stem-cell research is still in its infancy, considering all the reports that predict it could provide treatments — perhaps even cures — for life-threatening diseases such as Alzheimer’s, Parkinson’s and diabetes.

But Charles Jennings, executive director of Harvard University’s Stem Cell Institute, says there already have been some breakthroughs.

Researchers in Sweden and the United States have demonstrated, using dopamine transplants, “clear clinical” evidence of the promise stem-cell research holds for Parkinson’s patients, he said.

And in a study by Japanese scientists, published last week in the Journal of Clinical Investigation, stem cells taken from monkey embryos and implanted in the brain reversed some Parkinson’s symptoms in other monkeys. The researchers say their work supports arguments that stem cells taken from days-old embryos can be used to replace tissues damaged by a variety of diseases.

Mr. Jennings acknowledges that this progress has come amid controversy, especially in the United States.

“In some cases, the dopamine transplanted came from aborted fetuses,” and embryonic stem cells were used in some animal studies, he said.

Embryonic stem-cell research is fraught with moral controversy because it requires embryos to be destroyed, which many see as killing.

Some U.S. stem-cell researchers also expressed optimism about a study published in the December issue of the Journal of Cranio-Maxilliofacial Surgery. In the study, German scientists reported how stem cells from fat tissue were used to help grow bone to repair the damaged skull of a 7-year-old girl.

Dr. Roy C. Ogle, a stem-cell researcher and specialist in skull-reconstruction surgery at the University of Virginia, called the report a “landmark study.”

Meanwhile, Canadian researchers are working to show olfactory stem cells, those taken from deep inside the nose, can repair damaged spinal function in rats and mice.

Jane Roskams, a neuroscientist at the University of British Columbia in Vancouver, said the stem cells she is testing are like those derived from the embryo, but they exist in the noses of adult rats and mice. When the cells are grown in culture and transplanted into the damaged spinal cords of rodents, those injuries are repaired and the nerves regenerated, she said.

“When it comes to the nervous system, a rat is not a human. So we have to have safety and efficacy studies in animals first, and next there will be primate studies,” Miss Roskams said.

She said she recognizes many paralyzed patients are desperate for relief and that some have responded to ads on the Internet for unproven nose-to-spine transplants available in Portugal and China at prices ranging from $50,000 to $100,000.

“People are desperate. They hear the hype and the hope, and they go for it … but we have to prove first that these procedures are safe. We have to do it right,” Miss Roskams said.

In October, the Harvard institute stirred controversy when some of its scientists asked the university’s ethics committees for permission to clone human embryos in order to create stem cells for disease research. If the request is granted, Harvard researchers would be the first in the United States to do so.

The Harvard scientists would use a cloning technique known as somatic-cell nuclear transfer to create new embryonic stem-cell lines that have built-in genetic diseases. They foresee particular success with this technology in Alzheimer’s research, as well as studies of diabetes and Parkinson’s.

In addition, Douglas Melton, co-director of the institute, said last year alone, he isolated 28 new human embryonic stem-cell lines using private funding.

“Harvard is absolutely opposed to human reproductive cloning,” Mr. Jennings said. Nevertheless, he said he recognizes moral issues must be resolved in the therapeutic work Harvard wants to do, because embryos would be destroyed in harvesting the stem cells.

Excitement about the progress of stem-cell research was generated in the press in November, when South Korean researchers held a press conference to introduce a 37-year-old woman who was walking haltingly after 20 years of paralysis.

The woman called it a “miracle” that scientists had used stem cells from umbilical-cord blood to repair her damaged spine.

The findings received mixed reviews from those in the scientific community after it was revealed they had not been published in a peer-reviewed journal.

“One has to be cautious about interpreting anecdotal evidence in single patients. … One should be very cautious about predicting cures for spinal-cord injuries any time soon,” Mr. Jennings said.

Enthusiasm about the future of stem-cell research remains high in this country, based on the large amount of money being contributed to universities to pursue it and the $3 billion bond measure that California voters approved Nov. 2 to expand embryonic stem-cell research in that state.

The California proposition was approved, despite the fact that many Americans — led by President Bush — object to embryonic stem-cell research on moral grounds.

On Aug. 9, 2001, Mr. Bush ordered that federal funding for research be limited to embryonic stem-cell lines already in existence and that itnot be used on any new cell lines created from donated surplus embryos.

This freeze has prompted many institutions to engage in aggressive private fund-raising. Like California, more states are providing funding to help fuel more embryonic stem-cell research.

Harvard says it expects to generate contributions “in the tens of millions of dollars,” primarily from wealthy donors, to fuel its stem-cell research. It has shipped hundreds of samples of its embryonic stem-cell lines to scientists in countries such as Great Britain and Israel, where the research is less restricted.

Wisconsin Gov. James E. Doyle, a Democrat, recently announced that state and private funds would be used to build a $375 million research center on the University of Wisconsin’s Madison campus. It was at that location in 1998 that biologist James Thomson first isolated embryonic stem cells. New Jersey has provided $9.5 million to establish a stem-cell institute in that state.

While some encourage an expansion of embryonic stem-cell research, those in the pro-life community remain morally outraged. This has prompted them to endorse and promote adult stem cells as an alternative.

But there are still doubts about whether adult stem cells could be as effective as embryonic stem cells, which can develop into any kind of tissue in the body. Most research suggests cell differentiation is more limited with adult stem cells.

“We don’t believe adult stem cells can do everything embryonic stem cells can do. We think both have their place, and that’s why we’re working with both types of stem cells,” Mr. Jennings said.

For decades, long before the term “stem cell” became widely used, doctors have been transplanting bone marrow, which contains adult stem cells that form blood cells. The transplants have been used to treat certain cancers and other immune and blood disorders.

“Bone-marrow transplants have saved thousands of lives, and they are the prototype of stem-cell therapy. We’re hoping to replicate that kind of success with other stem cells,” Mr. Jennings said.

He said he is not aware of any cases in which embryonic stem cells have “given clear clinical benefits in human studies.” But he said it’s important to remember that they are “very new.”

Given the moral concerns about embryonic stem cells, much attention has been focused on trying to find ways to obtain large volumes of stem cells without killing or creating embryos.

In early December, the President’s Council on Bioethics, the panel that advises Mr. Bush on cloning and other bioethical issues, was presented with two proposals, both still experimental, for ending the political impasse that currently blocks embryonic stem-cell research.

In one technique, scientists would deliberately sabotage the “nuclear transfer” cloning process so the resulting bundle of cells is not an embryo. However, it still would have stem-cell precursors that could be removed and used.

In the other procedure, scientists would harvest cells from embryos created to treat infertility but that are no longer growing and are, in fact, functionally dead.

Meanwhile, there continues to be findings in research involving less-controversial adult stem cells. For instance, scientists at the University of Florida last year restored normal blood-sugar levels in diabetic mice for three months by chemically coaxing bone-marrow cells to produce insulin.

“The findings … demonstrate the importance of adult stem-cell research and could one day help combat a form of diabetes in humans,” said Bryon Petersen, an assistant professor of pathology, immunology and laboratory medicine at UF’s College of Medicine.

Last spring, other UF researchers showed that adult blood stem cells can convert to brain cells in humans. In research published in the British medical journal Lancet, Edward Scott and colleagues described how male blood stem cells evolved into male brain cells in three women who underwent bone-marrow transplants to treat cancer.

And last fall, the American Heart Association’s journal, Stroke, published results of a study in which umbilical-cord blood stem cells were used to treat stroke in animal models. The report by Georgia and Florida researchers found that stem cells taken from umbilical-cord blood, and then given intravenously along with a drug capable of breaking the brain’s protective barrier, can sharply reduce stroke size and damage.

When the procedure was used in the first hours and days after a stroke, stroke size decreased by 40 percent, and the resulting disability was significantly reduced, the researchers said.

Dr. Ogle said cord blood stem cells are an “intermediary” between fetal and adult stem cells. They are not considered controversial because they do not create embryos, and the placenta is discarded after birth.

David Prentice, senior fellow for life sciences for the Family Research Council, which advocates adult and cord blood stem-cell research, says a host of studies dating back nearly five years have indicated the stem cells can transform into brain neurons.

But there has been uncertainty in some other areas. For example, in 2001, a report in the journal Nature said bone-marrow cells could transform into heart muscle. This suggested such stem cells could offer hope for treating heart disease. But last spring, two other papers in the same British science journal suggested the original research was wrong.

“There is some question whether bone-marrow cells can make heart cells,” Mr. Prentice said. “But studies in animals showed that hearts got better [when marrow cells were used]. This could mean they worked by improving heart vessels or that they stimulate tissue to repair itself.”

Last fall, the U.S. Conference of Catholic Bishops ran a two-week print campaign promoting adult stem-cell research over embryonic stem-cell research.

Mr. Prentice says he remains convinced that adult stem-cell research will prove to be “more valuable” for therapeutic purposes.

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