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Minnesota company bets its future on adult stem cell research
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Rare adult stem cells from umbilical cord blood shown early in culture. (Photo Courtesy of BioE and the University of Minnesota )
The debate over embryonic stem cell research is expected to reignite in Washington when Congress returns from its summer break. A growing number of House and Senate lawmakers want to loosen President Bush's 2001 federal funding restrictions on the research. Embryonic stem cell studies are controversial because they require the destruction of human embryos. But many scientists say the research is vital because embryonic cells have an amazing ability to transform into all sorts of human tissue from bone to muscle to fat.

In contrast to embryonic stem cells, adult stem cells appear to be more limited in the types of tissue that they can be programmed to create. But increasingly, researchers are finding ways around some of those limitations. In Minnesota, a small biotech company called BioE says it has discovered an adult stem cell that appears to act a lot like embryonic stem cells. The company has cloned the rare cells and stockpiled millions of copies in its warehouse. Questions still remain about the science behind BioE's discovery. But the company is forging ahead with plans to sell its stem cells to researchers around the world.

Vadnais Heights, Minn. — BioE is located in a modest industrial park building in the St. Paul suburb of Vadnais Heights. Just inside the company's entrance, a tower of medical journals balances in a corner. Eventually it will touch the ceiling, if it isn't knocked over first.

Cubicles are cramped and covered in papers. Between them a narrow path leads to the lab, where BioE researchers discovered a rare type of stem cell.

Inside the lab, BioE founder and chief scientific officer Dan Collins scoots his chair up to a microscope and eagerly slips a demonstration slide under the lens.

"You can see the cells are kind of oddly shaped," says Collins. "They're kind of flat and stretched out and dark in color."

The cells are flat because they divided recently. Right next to them, Collins says, some plump yellowish stem cells are just about to divide.

The sight of these multiplying stem cells is a thrill to Collins. For years he couldn't even detect them. He finally noticed them after he developed a liquid that separates stem cells from other blood cells.

Even then, he says these cells are still extremely difficult to find.

"They are so rare in number. We are talking about, in typical blood that may have over a billion cells in it, we may find only 200 to 1,000 of these cells in that billion cells. So I believe that's why other groups have not found them yet," says Collins.

Not only are they rare, they're special. Collins says laboratory studies have shown that these stem cells appear to be easier to manipulate than some other types of adult stem cells.

With a little coaxing, Collins says he has been able to influence the type of tissue these cells mimic.

"We are able to turn them into cells that represent each of the so-called germinal layers of the embryo," says Collins. "And those reflect on the ability of us to potentially be able to turn them into every cell in the body -- once we learn the little tricks to get them to go down a particular pathway that will change them directly into a cell type."

Some of those little tricks include using chemicals to nudge the cells in a particular direction. So far, Collins has been able to get some of his stem cells to emit insulin just like a pancreas. He's gotten others to grow fibers just like muscle cells.

We are able to turn them into cells that represent each of the so-called germinal layers of the embryo. And those reflect on the ability of us to potentially be able to turn them into every cell in the body.
- Researcher Dan Collins

Other scientists have been able to do some of these things too. University of Minnesota researcher Catherine Verfaillie did it a couple of years ago with adult stem cells from bone marrow.

Collins believes BioE's stem cells have even more potential.

"We believe that these types of cells are actually more primitive and more flexible than the adult stem cells that would be found in bone marrow," says Collins. "They're much younger. They're more robust."

That's because they're found in the blood of umbilical cords. Most hospitals dispose of umbilical cord blood after a baby is born, but some set it aside for researchers. Collins thinks stem cells found in umbilical cords are more like embryonic stem cells. Embryonic stem cells easily transform in to all sorts of tissue types.

One thing he does know for sure is that BioE's stem cells are easy to grow. And that's where science has found a perfect match with business. BioE president Mike Haider says the future holds promise for his company.

"Duplicate copies of the stem of that cell can be grown up in large enough quantities to be of interest, not only to researchers, but potentially to therapeutic uses downstream," Haider says.

In just the past eight months, BioE has created 53 distinct stem cell lines and cloned millions of cells from each line.

So far, the company has distributed its cells to a few select researchers in the hopes that they will verify BioE's results. That would open the door for the company to sell its stem cells to scientists around the world.

At the Clinical Cell Therapy Laboratory at the University of Minnesota, technician Cheryl Adams studies several of BioE's cell lines. Adam's lab has agreed to test the company's findings, and possibly work with the company if the stem cells live up to BioE's claims.

"Right now I've just got three cell lines that are growing," says Adams. "We just keep splitting them to find out how many passages they'll go before they start dying off."

So far, Adams and her colleagues have been able to duplicate many of BioE's results.

Dr. David McKenna is an assistant medical director at the lab. On his office computer, he points to slides that show all the cells his team has been able to create with BioE's stem cells.

Each of the slides is dotted with fluorescent pink splotches.

"These are markers, alpha-actinin and fast skeletal myacin that mark for muscle cells, and they are lighting up as they have differentiated into muscle," says McKenna. "We've also then gone down bone (lines), and we actually have gone down neural and hepatic lines as well. And we've just started to try and repeat some of the cloning studies that BioE has already completed."

If these markers are accurate, it could mean that one day these stem cells could be used to rebuild bones or worn-out heart muscles in humans.

But McKenna and BioE researchers don't know if these cells will really go on to develop into the types of tissues they appear to represent. They will need to conduct animal studies, and eventually human studies, to find that out.

There are some who are concerned that so far BioE has not subjected its work to peer review. BioE has not published any of its research in scientific journals. Scientists consider that the gold standard for publicizing research discoveries.

Dr. Dan Kaufman, a member of the U of M's Stem Cell Institute, says he still has questions about BioE's research.

"I'm not saying that they're not getting the results that they say, but really, anybody can say that they have anything," says Kaufman. "And without sort of an independent, unbiased person looking at the data, people can often get fooled to see what they want to see rather than what's really there."

BioE acknowledges that it has not published its findings yet. But president Mike Haider says that's more a business decision than a scientific decision.

"We call ourselves an enabling company, so we are bringing stem cells to the clinicians, the scientists, the researchers. They are going to know the best uses of the material and they're also treating patients. BioE doesn't treat patients," says Haider. "And as a company we're not developing the end therapy. We're developing the tool that would be used in the therapy."

Haider says he hopes that scientists view BioE's stem cells as a possible alternative to embryonic stem cells, not necessarily a replacement. He says his company believes it's important to conduct research on both embryonic and adult stem cells.

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