U.S. Embryonic Stem Cell Lines Contaminated
By E.J. Mundell
SUNDAY, Jan. 23 (HealthDayNews) -- In what could prove to be a setback for an already controversial area of research, scientists say all federally approved lines of embryonic stem cells are contaminated with a non-human molecule.
Because the human immune system typically seeks out and destroys cells bearing this molecule, therapies using the contaminated stem cells may fail, explained researcher Dr. Ajit Varki, a specialist in cell biology at the University of California, San Diego.
"Even worse, in the process of killing the contaminated cells, the patient might have a bad reaction," Varki explained. "It could be like receiving a bad blood transfusion."
The full details of the study are published in the Jan. 23 issue of Nature Medicine after being outlined to a panel of stem cell experts at the National Academies of Science in October.
The findings could put the brakes on a type of research already under fire from conservative policymakers in the United States, experts said.
"This is going to slow things down in embryonic stem cell research," said stem cell researcher Paul R. Sanberg, director of the Center for Excellence for Aging and Brain Repair at the University of South Florida College of Medicine, in Tampa.
"People will need to now take this into account, not just for the lines previously used but for cell lines around the world, as well as those in the U.S.," he added.
The building blocks of life, stem cells have the ability to grow into a diverse range of tissue cells including bone, muscle, organs or even brain and nerve tissue. Cells sourced from human embryos have proven especially useful in this regard. For medical researchers, the ultimate goal is to use stem cells to replace tissues lost to such diseases as Alzheimer's, cancer or heart disease.
However, many in the United States oppose the harvesting of embryonic stem cells on moral grounds, pointing to the embryo as the first stage of human life. Current Bush Administration policy limits embryonic stem cell research to just the cell lines derived before Aug. 9, 2001.
Varki's research now suggests those lines may not prove useful as therapeutic agents.
To increase the number of stem cells available for use, scientific labs typically immerse the cells in a nutrient-rich biological bath. "They use cells from mouse embryos, called 'feeder cells,'" Varki explained. "They also put -- as in most culture mediums -- serum [blood] from animals to help grow the cells."
According to Varki, those animal cells can be a source of unwanted contamination. All living cells carry a dense outer coating of sugar molecules, including compounds called sialic acids.
"There's one sialic acid, called Neu5Gc, you find it on the surface of cells from pigs, dogs, mice, chimpanzees," Varki said.
At some point in human evolution, people lost the ability to add Neu5Gc to the outsides of their cells, however. In fact, Varki added, human immune systems now recognize the molecule as "alien" and automatically attack Neu5Gc-bearing cells.
In his research on these surface compounds, Varki discovered human cells appear to pick up Neu5Gc whenever they are in proximity to animal cells.
"We knew that was happening in normal cultured human cells, so we thought 'Gee, maybe this could be happening in the embryonic stem cells,'" he said.
Close inspection in the laboratory proved that all U.S. embryonic stem cell lines currently used in research have picked up Neu5Gc during the culturing process, Varki said.
"In their current form, therefore, if this problem isn't solved, putting embryonic stem cells into humans in some form of treatment will probably result in some kind of immune reaction against the cells, in most humans," Varki said.
He stressed that the federally approved lines remain useful for in vitro or animal studies in the lab. Furthermore, the discovery of Neu5Gc contamination shouldn't invalidate the results of any stem cell research done to date, Varki said.
However, the finding should spur research into new, uncontaminated sources of embryonic stem cells for use in humans.
"This is yet another reason to look at non-embryonic [adult] stem cell sources, such as umbilical cord blood, bone marrow, fat cells, other types," Sanberg said.
While adult stem cells may not always be as easily manipulated as embryonic cells, they can often be harvested and transplanted whole, without the need for culturing, he added.
And Sanberg said scientists are still not sure whether embryonic stem cells need to survive over the long term in the human body to work their magic.
"A lot of us think stem cells work by providing chemicals like growth factors, cytokines, other compounds, to enhance the body's own repair mechanisms," he said. "If that's the case, putting in cells that don't last might be ok -- the new donor cells will be gone, but the host cells will have responded."
Researchers are also hard at work developing new methods of culturing stem cells without animal-cell contamination. For example, Varki's lab has developed a strain of mice with human-like cells that do not pick up Neu5Gc. Using feeder cells from these mice in the culture medium may be "another long-term solution," Varki said.
"Someday, of course, you'd like to see embryonic stem cells grown in serum from the person who's going to receive them," he said. "But that's still a long ways away."
"Theoretically, it's possible to get around this problem, but it raises more general questions," Varki added. "This is just one example of a problem using animal cells -- who knows what else is going on? It's telling us to be cautious. Don't think that just because we can solve this problem we've solved all the problems."
More information
To learn more about stem cells and stem cell research, head to the International Society for Stem Cell Research.
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