Published online: 24
January 2005; | doi:10.1038/news050124-1
Human stem cells trigger immune attack
Doubt cast on therapeutic
use of embryonic cell lines.
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.
Exposure to molecules from
animals might have made human stem cells
ANDREW LEONARD / SCIENCE PHOTO
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.
found a serious problem," says Ajit Varki, a cell biologist at
the University of California, San Diego.
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
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.
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.
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
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
| We need to take caution when
using these cells as therapeutics. |
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
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
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.
- Martin, M., Muotri, A., Gage, F. & Varki, A.
Nat Med. 11, 228−232 doi:10.1038/nm1181