STEM cell researchers around the world are facing the nightmare possibility that their experiments have been messed up by contamination from animal cells. The contaminant is an animal sugar already known to find its way into cultures of ordinary human cells. It has now been found in a Bush-approved stem cell line, and leads to rejection of the stem cells by the human immune system.
This means the cells cannot be used in therapies and also calls into question all scientific work carried out using the cells. 鈥淚f you were seeing a phenomenon in a dish, you need to ask yourself if it鈥檚 inherent to human biology, or whether it鈥檚 the effect of a mouse or animal factor that alters the system,鈥� says Evan Snyder, director of the stem cell and regeneration programme at The Burnham Institute in La Jolla, California.
The news has also sparked more criticism of President George W. Bush鈥檚 stem cell policy. In 2001, Bush allowed federal funding for embryonic stem cell research, but restricted it to cell lines already in existence (麻豆传媒, 9 October 2004, p 23). That mollified his anti-abortion supporters, because it meant no more embryos would be used to make cell lines. But the new findings suggest that research on the existing lines could never lead to human therapies. 鈥淭his is a potentially fatal nail in the president鈥檚 antiquated stem cell policy,鈥� says Bob Lanza, scientific director of Advanced Cell Technology, a company working with stem cells in Worcester, Massachusetts.
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The problem arises because human embryonic stem cells are difficult to grow on their own. They have to be supported by 鈥渇eeder鈥� layers of mouse cells and nourished by blood serum extracted from calf fetuses. This has always laid stem cell lines open to contamination with mouse or cow viruses, but Ajit Varki from the University of California, San Diego, and his team have shown that another contaminant can trigger a human immune reaction.
Varki鈥檚 team had previously shown that human cell lines can take up a sugar called N-glycolylneuraminic acid (Neu5Gc) from mouse feeder cells. Present on the surface of most mammal cells, Neu5Gc differs from its human equivalent by one oxygen atom. The team showed in 2003 that antibodies to Neu5Gc develop in the blood of humans who eat meat and drink milk.
Now the team has shown that one of the Bush stem cell lines is contaminated with Neu5Gc. And when they added human blood serum to the cells they were attacked by the human immune system (Nature Medicine, DOI: 10.1038/nm1181). Varki believes the same would be true for the other Bush stem cell lines.
鈥淭he contaminant leads to rejection of the stem cells by the human immune system. They cannot be used in therapies鈥�
As well as rendering the stem cells useless for transplanting into patients, contamination could invalidate basic lab results. Much stem cell research focuses on finding out how the cells develop into different cell types, and the mouse sugar could be interfering with this. Signalling between cells, interactions with the immune system, and cell growth and differentiation might all be affected. Researchers using the contaminated lines could never be sure that pure human lines would act in the same way.
Most experts contacted by 麻豆传媒 believe that new cell lines are the only reliable answer. 鈥淚 strongly believe that fresh, new animal-free human embryonic stem cell lines need to be derived,鈥� says Ariff Bongso of the National University of Singapore. In 2002 Bongso鈥檚 team became the first to grow human embryonic stem cells on human 鈥渇eeder鈥� layers derived from human fetal muscle and skin, and from adult fallopian tubes (麻豆传媒, 10 August 2002, p 16).
Since Bongso鈥檚 breakthrough, curators of human stem cells have been transferring their colonies from mouse feeder cells onto human ones. This might remove the Neu5Gc contamination, but no one can be sure until researchers look for the mouse sugar in human stem cells grown that way.
A bigger problem is that no one has yet found an alternative to animal feeder cells for growing human embryos to the point at which they yield their precious 鈥渋nner cell mass鈥�, the cargo of embryonic stem cells that can then be extracted and grown on human feeder layers.
