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Human stem cells trigger immune attack

January 24, 2005 By Jessica Ebert This article courtesy of Nature News.

Doubt cast on therapeutic use of embryonic cell lines.

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Most human embryonic stem-cell lines, including those available to federally funded researchers in the United States, may be useless for therapeutic applications. The body's immune defences would probably attack the cells, say US researchers.

When embryonic stem cells are added to serum from human blood, antibodies stick to the cells. This suggests the cells are seen as foreign, and that transplanting them into the body would trigger the immune system to reject them.

"We've found a serious problem," says Ajit Varki, a cell biologist at the University of California, San Diego.

The difficulty arises from the way human embryonic stem cells are grown and maintained in the lab. Scientists grow stem cells in petri dishes containing nutrient broth and other cells. These feed the stem cells, and give them a place to attach themselves.

Feeder cells are typically embryonic cells from mice and nutrient broth usually contains animal serum. These mouse cells have a molecule on their surface called N-glycolylneuraminic acid or Neu5Gc.

Varki's team had already found that human embryonic stem cells take up Neu5Gc; they now show that humans react against it. Eating red meat and dairy products has sensitized people to the molecule, Varki says. The team reports its latest finding in the February issue of Nature Medicine1.

Growing pains

We need to take caution when using these cells as therapeutics.
Fred Gage
The Salk Institute,La Jolla, California
Scientists have long worried about the risks of growing human embryonic stem cells in the presence of animal-derived substances. "Now we've identified an actual reason for being concerned," says Fred Gage, a neurobiologist at the Salk Institute for Biological Studies in La Jolla, California, and a member of the team.

This does not mean that existing cell lines should be abandoned. "We're not saying that all available lines should be thrown out," Gage says. But, he adds, "we need to take caution when using these cells as therapeutics". Using US federal money to create new stem-cell lines is currently forbidden.

Varki's team did not test all of the 22 federally funded human embryonic stem-cell lines that were created in the United States before the ban came down. But the cellular mechanism for absorbing Neu5Gc is universal, and all US stem-cell cultures have probably been exposed to animal material. "I find it hard to imagine that any of the other lines would be free of this contamination," Varki says.

The current stem-cell lines have little clinical value, but that is "not an issue for pursuing basic research", says James Battey, chairman of the National Institutes of Health's stem-cell task force. In fact, these lines will help to develop animal-free conditions for growing and maintaining human embryonic stem cells and minimizing safety concerns, he says.

Until better growth conditions are established, explains Battey, a group in Sweden with stem cells that have never been exposed to materials from animals will keep the cells frozen and unavailable for use.

References

  1. Martin, M., Muotri, A., Gage, F. & Varki, A. Nat Med. 11, 228–232 doi:10.1038/nm1181 (2005).

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