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Stem Cell Advances in Rodents May Benefit Humans

Use of adult stem cells would eliminate need for embryonic cells

THURSDAY, June 20, 2002 (HealthDayNews) -- A new form of stem cells taken from mature tissue appears to be as versatile, if not more so, than those derived from embryos.

Research reported in the current Nature paints the most promising picture yet of the virtues of so-called adult stem cells, which can in theory become virtually any tissue in the body. Although these new cells behave like embryonic stem cells, they don't require the destruction of embryos, a major ethical morass.

In a second paper, also published this week in Nature, scientists say they have treated a rat version of Parkinson's disease with embryonic stem cells from mice. With the right mix of chemicals, these cells can be coaxed into becoming neurons that produce dopamine, the brain messenger molecule that's deficient in the neurologic disorder.

When transplanted into the brains of the rats, these new neurons seem to function normally, and the ailing animals show signs of improvement in motor trouble.

"This is not a cure," says Ronald McKay, a stem cell expert at the National Institute of Neurological Disorders and Stroke and a co-author of the study. "But it's absolutely definitive evidence that these cells work in the brain."

Equally important, McKay says, his group is now able to generate at will large quantities of dopamine-producing neurons from the mid-brain region of rodents. These cells are crucial players in a healthy dopamine system.

"We're absolutely confident that we have the right kind of cell here," says McKay.

The first study was led by Dr. Catherine Verfaillie, director of the University of Minnesota Stem Cell Institute in Minneapolis. Verfaillie and her colleagues showed that stem cells purified from adult rat and mouse bone marrow could go on to become all three primary tissue types. These are endoderm, ectoderm and mesoderm, which in embryos are the reservoirs for the cells that ultimately differentiate into the various organs.

In both lab dishes and mice, the essentially immortal stem cells were coaxed into becoming a full range tissues, including muscle, fat, cartilage, liver and even brain.

In follow-up experiments, Verfaillie's team seeded early stage mouse embryos with the adult stem cells, which they've dubbed multipotent adult progenitor cells (MAPCs). With the help of blue-tinting gene tracer, the researchers found that when the animals developed, some had about 40 percent of their tissues derived from MAPCs.

They also infused grown mice with MAPCs, and saw a somewhat more limited take-up of the cells.

Verfaillie's group has conducted similar experiments using MAPCs derived from human bone marrow, with encouraging early results. So far, they have injected as many as 100,000 stem cells, including some from people, into mice with no evidence of tumors in up to a year of observation.

MCAPs are extremely scarce in humans, perhaps one in 1,000,000 marrow cells, Verfaillie said, though they appear to be about 10 times more common in young people than in old. However, her group has been able to dig up the cells in the bone marrow samples of roughly 80 percent of volunteers.

Earlier this year, scientists in the United States and Britain reported that previous experiments with adult stem cells may have overstated their versatility. In fact, the researchers argued, the tissues they go on to generate may arise from spontaneous fusion of adult stem cells with other cells, and not from the stem cells themselves. What's more, the mergers create cells with twice the normal number of chromosomes, and with unknown implications for the health of patients who might receive them, the researchers contend.

Verfaillie's group says it was able to rule out cell fusion in their test dish studies, and the spawned cells had normal chromosomes.

Yet Dr. Naohiro Terada, one of the researchers who exposed the potential problem, says that doesn't rule out the possibility that fusion might occur when the stem cells are grafted into living creatures.

"I don't think it's totally excluded," says Terada, a pathologist at the University of Florida.

Verfaillie says the next step for her group is to see if it can generate functional tissues and organs by grafting human adult stem cells into mice. Another prospect for the cells is to use them as therapeutic vehicles to shuttle corrective genes into tissues with protein defects.

Defective proteins have been linked to diseases ranging from Alzheimer's disease to muscular dystrophy.

For McKay, the coming challenge will be to bring the embryonic stem cell experiments from rodents to primates -- and if that succeeds, to people. That could take at least five years and possibly more, and only if we have the "collective will and dedication," he says.

President Bush has strictly curtailed research on embryos, including embryonic stem cells, so any advance with adult stem cells is seen as a potential end-run around this barrier. However, both Verfaillie and McKay say their work was complementary and neither discovery obscured the importance of pursuing both forms of cell types.

"It's a field that should cross-fertilize itself," Verfaillie says.

What To Do

To learn more about what's realistic to expect from stem cells, check the Batten Support & Research Trust. You can also visit the National Institutes of Health, or the Society for Developmental Biology.

SOURCES: Catherine Verfaillie, M.D., director, University of Minnesota Stem Cell Institute, Minneapolis; Ronald McKay, Ph.D., National Institute of Neurological Disorders and Stroke, Bethesda, Md.; and Naohiro Terada, M.D., Ph.D., associate professor, University of Florida, Gainesville; June 23, 2002, Nature
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