Artery Newest Stem Cell Source

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http://my.webmd.com/content/article/76/89948.htm

 

Artery Newest Stem Cell Source

 

Shape-Shifting Cells Can Become Bone, Cartilage, Muscle, or Marrow

 

By Daniel DeNoon

WebMD Medical News Reviewed By Brunilda Nazario, MD

on Monday, October 27, 2003

 

 

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Oct. 27, 2003 -- One day, doctors may treat bone loss with cells harvested from your arteries.

 

 

It could happen, now that researchers have discovered a new population of stem cells. The finding explains why -- for centuries -- butchers have sometimes found bones growing inside blood vessels.

 

 

It also explains hardening of the arteries, says Linda L. Demer, MD, PhD. Demer led the UCLA team that discovered what the cells can do.

 

 

"The reason that arteries harden is that bone is growing in them," Demer says in a news release.

 

 

Demer's team previously showed that this bone doesn't come from someplace else in the body. They traced the bone growth to calcifying vascular cells or CVCs, found in the artery walls and heart valves. Unlike normal cells, CVCs can turn into other kinds of cells.

 

 

"We have now shown clearly that CVCs not only become bone but cartilage, marrow, and smooth muscle as well," Demer says. The new findings appear in the Oct. 28 early access issue Circulation: Journal of the American Heart Association.

 

 

And they have one extra trick: They can self renew, thus representing a lifelong source of new bone and cartilage cells.

 

 

On the other hand, CVCs can't turn into fat cells. But that may be a big advantage if the cells can be harvested, grown to larger numbers, and used to treat disease.

 

 

"Older women who are losing bone in their skeletons are still forming fresh new bone in their [heart artery]," Demer says. "That suggests they still have the capacity to create bone. It may be possible to harness that process to create a therapy for bone loss."

 

 

 

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SOURCES: Tintut, Y. Circulation: Journal of the American Heart Association, early access issue, Oct. 28, 2003; vol 108. Press release, American Heart Association.

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November 3, 2003

Icelandic Company Says It Has Found Osteoporosis Gene

By NICHOLAS WADE

 

gene linked to osteoporosis has been identified by Decode Genetics, the Icelandic company that is leading efforts to find the genes that underlie common human diseases.

 

People with any of three specific variants of the gene have a threefold risk of developing the disease, which is characterized by brittle bones.

 

A test for the variant forms of the gene is being developed by Roche Diagnostics and will be available in diagnostic laboratories at the beginning of next year, said Dr. Kari Stefansson, chief executive of Decode. The test need be taken only once in a lifetime, and if a gene variant were found, a high-calcium diet and plenty of exercise would be prescribed, Dr. Stefansson said.

 

Other genes have been linked to osteoporosis, but results vary from one population to the next. The new gene could be the first consistent contributor to the disease if its link, found so far in three populations, holds worldwide. The finding is being published today in the new online journal Public Library of Science.

 

Osteoporosis is an increasingly common disease as the population ages. It affects both sexes but particularly women after menopause. There are more than a million bone fractures a year in the United States from osteoporosis.

 

The new finding comes at a time of particular difficulty for doctors trying to treat the disease. Supplements of estrogen, a hormone that dwindles at menopause, prevent bone loss effectively, but a group of researchers recommended last month that estrogen not be prescribed solely to treat or prevent osteoporosis because of the slightly increased risk of breast cancer for those who take it. The Food and Drug Administration has not yet issued an opinion on the issue.

 

None of the available alternatives to estrogen is ideal, and the new gene found by Decode may help the search for better drugs.

 

The Decode team, led by Dr. Unnur Styrkarsdottir, scanned the genomes of 207 Icelandic families with at least one member who had both low bone-mineral density and bone fractures. Searching for stretches of DNA that the patients might have inherited in common, the Decode team identified a gene on Chromosome 20 called BMP-2, for bone morphogenetic protein-2.

 

The BMP-2 gene exists in several versions that differ very slightly in their sequence of DNA units. The Decode team found that three of these versions presented a particular risk for osteoporosis, since 30 percent of their patients had one or another of them. Carrying one of these versions does not guarantee that a person will develop osteoporosis, but it does make the risk three times as great, Dr. Stefansson said.

 

A major question is how far the Icelandic findings will prove true in other populations. Iceland was populated from the 10th century onward by vikings from Norway who had picked up several wives apiece from Ireland. Though disease genes found in Iceland are always relevant elsewhere, Dr. Stefansson said, the population tends to have fewer variants of each gene. To capture all such variants with a diagnostic test, the gene needs to be studied elsewhere.

 

Dr. Stefansson said the link between the BMP-2 variants and osteoporosis had been confirmed in a Danish population and was in the process of being validated in the United States in a group of women who have been studied for many years at the University of California at San Francisco.

 

Experts in bone loss tend to be skeptical of claims that specific genes are involved in osteoporosis, because several past claims have proved exaggerated.

 

"So this is one more of a long list," said Dr. Lawrence G. Raisz, chairman of the National Osteoporosis Foundation's scientific advisory board. "Not until much larger studies are done can we even guess. But it's exciting."

 

Apart from the statistical genetics that support the finding, the Decode result is intuitively plausible: the company conducted an impartial search of the whole human genome and alighted on a gene that was known independently to enhance bone formation.

 

"I love this stuff," said Dr. Gregory Mundy, an osteoporosis expert at the University of Texas Health Science Center, who has been studying drugs that stimulate the BMP-2 gene. "It supports what we have been doing for a number of years and gives it good credence."

 

An available measure for the weakening of the bones is called the bone mineral density test, or B.M.D. But the test has been criticized because everyone starts to lose bone strength after a certain youthful peak, and many people have a low score but do not get fractures. Bone density, it seems, does not fully reflect bone quality.

 

Dr. Stefansson said the test based on BMP-2 would be more useful because it was more predictive. Whereas the density test shows the state of a person's current mineral loss, which may or may not lead to fractures, a positive gene test, taken at any time in a person's life, would indicate a definite risk and would dictate that the patient follow a diet and exercise regimen to allay it, Dr. Stefansson said.

 

Finding the genes that underlie the common diseases was a central justification of the Human Genome Project, the multiyear effort to sequence the genome. By combining knowledge of the sequence with the special features of the Icelandic population, Decode Genetics has taken a substantial lead in tracking down the variant genes that cause such diseases.

 

So far the company has discovered 15 such genes, Dr. Stefansson said. Descriptions of four have now been published in scientific journals, and an additional 11 are awaiting publication.

 

 

 

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