Embryonic stem cell line found to be contaminated
■ The NIH Stem Cell Task Force chair said the discovery may lead to congressional hearings.
By Andis Robeznieks — Posted Feb. 14, 2005
New calls for expanding the number of embryonic stem cell lines were sounded after University of California, San Diego, researchers identified an animal molecule that has contaminated one of the stem cell lines in the National Institutes of Health stem cell registry.
The contamination is believed to have occurred because the stem cell line in question was cultured using a layer of mouse cells. Since all the stem cell lines in the NIH registry have been grown using either mouse or fetal calf cells, they all are believed to be contaminated in the same way.
The UCSD researchers noted that many people have antibodies that attack the contaminating molecule -- N-glycolyneuraminic acid -- so any tissues developed using contaminated stem cells may result in a "deleterious immune reaction and/or rejection of the transplanted cells."
In the study, published online in the journal Nature Medicine on Jan. 23, researcher Ajit Varki, MD, and colleagues conclude that "it would be safest to start over again with newly derived [human embryonic stem cells] that have never been exposed to any animal products containing Neu5Gc and ideally, only ever exposed to serum from the intended transplant recipient. The current regulatory climate in the United States precludes this type of approach when using federal grant dollars."
Some critics of the Bush administration stem cell policy, which limits government funding for embryonic stem cells to existing lines, have taken this as a call to scrap the NIH registry and start all over, but Dr. Varki said that was not their intention.
"We are not saying that the existing approved lines are useless for further research," Dr. Varki said in an e-mail. "We are only saying that there are concerns about putting them into living humans, because of the potential for immune reactions and/or rejection. Prior to taking that step, this problem either needs to be solved -- or alternate lines need to be generated that are free of this problem."
James F. Battey Jr., MD, PhD, who chairs the NIH Stem Cell Task Force, said it had long been suspected that using animal feeder cells to culture stem cells may lead to contamination, so he was grateful to Dr. Varki for identifying the source of contamination. "Having a molecular identity for this helps us get a handle on monitoring it," Dr. Battey said. "But I disagree that cells derived from these stem cell lines will be rejected."
Dr. Battey said humans ingest Neu5Gc in meat and dairy products without experiencing immune responses. He added that the Food and Drug Administration had approved other health care products with animal molecules, and humans have been able to take those "with no evidence of rip-roaring immune rejection."
The report was bad news for three stem cell-related firms whose stock prices fell after the report's release. One, Rhode Island-based MultiCell Technologies, issued a news release announcing that it only uses adult stem cells, so it's not affected by embryonic stem cell line contamination.
Dr. Battey emphasized that any medical treatments using embryonic stem cells are still years away from human trials and stem cell lines in the NIH registry are suitable for the basic research that still needs to be done.
"This reminds me of the discussions around genetically modified vegetables with a lot of people saying a lot of things without a lot of analysis and data," Dr. Battey said. "We really need to stay factual in an area that is as emotionally charged as human embryonic stem cell research."
Still, he admitted that this new controversy will not settle down any time soon. "It wouldn't surprise me if we had congressional testimony on this," Dr. Battey said.
Jeffrey Kahn, PhD, MPH, director of the Center for Bioethics at the University of Minnesota Twin Cities Academic Health Center, said identification of Neu5Gc confirms the widespread suspicion that stem cell lines cultured with animal feeder cells were contaminated, and it gives ammunition to Bush administration critics.
"I think it will add impetus to the need to create additional [embryonic stem] cell lines," Dr. Kahn said. "The identification adds fuel to the fire for why we need additional stem cell lines -- unless they're able to figure out how to remove that protein from existing stem cell lines."
Dr. Battey said it may be possible for Neu5Gc to be diluted out of the stem cell lines by growing them in a culture free of animal cells for 10 to 20 generations.
Some new stem cell lines, created after Bush's Aug. 9, 2001, cutoff date, were not grown using animal cells, but Dr. Varki and colleagues said they may not be free from problems, either.
"Of course, the use of an 'all-human' environment carries a different set of risks (unexpected contamination with novel or newly emerging pathogens)," they wrote in the Nature Medicine report.
AMA policy supports the use of therapeutic cloning technology for biomedical research and encourages strong public support for federal funding of stem cell research.