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Original Contribution
February 16, 2005

Human Embryonic Stem Cells Contaminated

JAMA. 2005;293(7):783-789. doi:10.1001/jama.293.7.789

While many scientists have been searching for medical breakthroughs with human embryonic stem cell (HESC) lines approved for study under federal funding in the United States, research published in the January 23 online issue of Nature Medicine (http://www.nature.com/naturemedicine/) revealed that these cells may be unsuitable for therapeutic use in humans. Findings by investigators at the University of California, San Diego, and the Salk Institute in La Jolla, Calif, could cast a shadow over many research endeavors across the country.

It is standard practice to culture HESCs with animal-derived materials, including connective tissue cells (called feeder layers) from mice and fetal calf serum. Unfortunately, the practice contaminates the HESCs with the nonhuman, cell surface sialic acid called N-glycolylneuraminic acid (Neu5Gc), the study showed. The investigators detected the presence of Neu5Gc on the cell surfaces of HESCs through the use of probes and a technique called electrospray mass spectrometry.

As they do not express Neu5Gc, humans have naturally occurring antibodies directed against the molecule. The researchers found that HESCs contaminated with Neu5Gc were recognized as foreign and were attacked by human antibodies. Therefore, any of these cells transplanted into patients for therapeutic purposes would potentially be rejected.

One solution to this obstacle might be to eliminate such animal products from cultures and instead use human serum and human-derived feeder cells. But there has been little success with such attempts, and the use of an “all-human” environment carries its own risks such as contamination with newly emerging pathogens, the investigators stated. In addition, it may be impossible to completely eliminate Neu5Gc, because it has become metabolically incorporated into the contaminated HESCs. The authors therefore suggest that it would be safest to obtain newly derived HESCs that have never been exposed to any animal products. But “the current regulatory climate in the United States precludes this type of approach, when using federal grant dollars,” they wrote.

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