Study Says All Stem Cell Lines Tainted

All human embryonic stem cell lines approved for use in federally funded research are contaminated with a foreign molecule from mice that may make them risky for use in medical therapies, according to a study released Sunday.

Researchers at UC San Diego and the Salk Institute for Biological Studies in La Jolla report that if the stem cells are transplanted into people, the cells could provoke an immune system attack that would wipe out their ability to deliver cures for diseases such as Parkinson’s, Alzheimer’s and diabetes.

The finding is a setback to the Bush administration’s controversial policy that provides federal funding only for research using embryonic stem cell lines that were created before August 2001. Evidence that all such lines are contaminated supports long-standing concerns among researchers that the lines eligible for federal money are insufficient to propel research forward.

The scientists who wrote the study say it could take at least a year or two -- if it is possible at all -- to find a way to salvage the stem cells by wiping them clean of the mouse molecules.

“We don’t know, but I’m trying to be optimistic,” said Fred H. Gage, a professor of genetics at the Salk Institute who co-wrote the paper in the current issue of Nature Medicine.

The researchers said the safest course was to create fresh batches of stem cells that were free of contamination from animal molecules -- a process that could also take years.

The need to develop new, uncontaminated embryonic stem cell lines would bolster the influence of the California Institute for Regenerative Medicine, a $3-billion funding agency established by state voters in November to circumvent President Bush’s restrictions.

“This is why Prop. 71 is so important,” Susan Fisher, a UC San Francisco professor of cell and tissue biology, said of California’s stem cell research measure. “We will be able to do this basic research to be able to really produce a strong foundation on which this work can continue.”

The new state agency allows the creation of new stem cell lines and will fund about $300 million a year in embryonic stem cell research for the next decade -- more than 10 times the yearly spending at the federal level. The initiative marks the largest state investment in basic scientific research, an area traditionally funded by the National Institutes of Health.

The stem cell lines allowed under Bush’s policy came from embryos donated by couples who no longer needed them for in vitro fertilization. In his 2001 address, Bush said: “This allows us to explore the promise and potential of stem cell research without crossing a fundamental moral line.”

From the start, however, researchers questioned the viability of the Bush-approved stem cell lines. The president said more than 60 such lines existed worldwide. About 20 lines proved usable, although concerns persisted about the techniques that had been used to create and keep them alive.

When the stem cells were first isolated, they were grown in petri dishes lined with cells from mice and bathed in blood serum from calves and other animals. The animal material was used to encourage the stem cells to multiply while preserving their unusual ability to mature into any kind of human cell.

This “pluripotency” is why embryonic stem cells have been so promising for both researchers and patients. For example, doctors could treat patients with juvenile diabetes by growing replacements for islet cells that fail to make insulin.

Researchers have suspected that exposing the stem cells to animal products could have contaminated them with viruses, proteins or other molecules that could be dangerous to people. Now they have evidence it did.

According to the study, human stem cells have incorporated a type of sialic acid that is common in many mammals but isn’t produced by people.

Potential contamination of the lines was discussed by Gage in October when he spoke to a National Academy of Sciences panel drawing up ethical guidelines for such research.

When the acid, Neu5Gc, enters the human body -- typically by eating meat or drinking milk -- antibodies rush to attack it.

Dr. Ajit Varki, a professor in UC San Diego’s department of cellular and molecular medicine, questioned whether stem cells containing the acid would also be vulnerable to attack if transplanted into humans. He and his colleagues exposed the stem cells to human blood serum that contained Neu5Gc antibodies.

“It kills the cells,” said Varki, one of the authors of the study. “It’s reasonable to assume the same thing would happen inside people.”

The most straightforward solution would be to start again with new stem cell lines.

“If none of these funding issues and legal issues and ethical and moral issues existed, then it would make sense to start over,” Varki said.

But to develop new lines, scientists must destroy 5-day-old embryos. Some religious leaders, social conservatives and others oppose the practice, saying it is tantamount to murder.

Bush’s research restrictions have come under sharp attack from high-profile figures including former First Lady Nancy Reagan and actors Christopher Reeve, who died in October, and Michael J. Fox. The issue took center stage in last year’s presidential campaign, and although Bush won reelection, advocates scored a victory with the passage of California’s Proposition 71.

Since then, lawmakers in several other states, including Wisconsin, New York and New Jersey, have announced major funding proposals in part to keep top researchers and scientists from going to California. Even before the influx of money from states, many leading researchers chose to forgo federal funding, instead getting private grants that allowed them to create new embryonic stem cell lines.

Fisher said the other strategy of cleansing existing stem cells of the mouse acid might solve the immediate problem. But there is still the possibility that there are other animal molecules that could alter the cells and make them unsuitable for human use.

“Many people have been very uncomfortable with the derivation of human cell lines using mouse [cells] and animal proteins,” said Fisher, who was not involved with the research published Sunday. “This is like being able to put your finger on why you’re paranoid.”

Times staff writer Megan Garvey contributed to this report.