Embryonic Stem Cells Found to Acquire Mutations

By Rick Weiss
Washington Post Staff Writer
Monday, September 5, 2005

Human embryonic stem cells, treasured by researchers because of their potential to help rejuvenate ailing organs, do not remain as ageless and perpetually unblemished as scientists once thought, according to a new research report.

Like ordinary cells, stem cells accumulate significant numbers of mutations over time, including several that could cause them to become tumors.

The findings, reported by an international team of scientists yesterday, could bolster those who have been calling upon President Bush to allow the use of federal money to create fresh stem cell colonies.

Embryonic stem cells, obtained from days-old human embryos, can morph into all kinds of tissues. They divide repeatedly in laboratory dishes, churning out self-replenishing colonies indefinitely -- a trait that has lent them a reputation as virtual fountains of youth.

Researchers hope to harvest batches of the cells periodically from master colonies and turn them into various kinds of tissues for transplantation into patients.

But the longer stem cells are cultivated -- and the more cell divisions they undergo -- the more mutations build up in their genes, Aravinda Chakravarti of Johns Hopkins Medical Institutions and his colleagues reported in yesterday's issue of the journal Nature Genetics.

The team measured the number of mutations and other DNA abnormalities in nine colonies of cells approved for use by federally funded researchers and compared the extent of the abnormalities before and after each lineage was subjected to a dozen or more rounds of cell division.

Previous efforts using relatively crude tools had found little evidence of changes, leading some scientists to conclude that the cells were largely protected from the ravages of everyday genetic wear and tear. But using sensitive "gene chips" that can identify subtle molecular changes in thousands of genes simultaneously, the team found that several colonies harbored increasing numbers of mutant cells over time.

Some of the mutations are known to play a role in transforming normal cells into rapidly dividing cancer cells. With that growth advantage, such cells can quickly outnumber others in a colony. Transplanting such cells into a patient could cause more medical problems than they would be likely to solve, scientists said.

Chakravarti warned that the work needs to be confirmed by additional experiments. "But if it turns out these cells really do become unstable over time," he said, "then that would put limits on the practical life spans of the cells and their usefulness for therapeutic purposes."

It is not known whether embryonic stem cells accumulate mutations to a greater or lesser extent than other cells in laboratory cultures. Chakravarti and others said they suspect that adult stem cells -- touted by some as a more ethical alternative to embryonic cells, whose retrieval requires the destruction of human embryos -- probably share the problem. No studies have been done.

Scientists also emphasized that the new study says nothing about which of the various lines analyzed are superior to others, because each was grown under different conditions. An even-playing-field comparison of embryonic stem cell lines is underway at the National Institutes of Health.

But the work does suggest that it might be necessary to test stem cells carefully before using them in treatments, to make sure they have not acquired potentially dangerous mutations, several scientists said.

Research to better understand the genetic stability of stem cells would be helped, several scientists added, by loosening Bush's restrictions on the use of federal funds for such studies.

The House has passed a bill that would do so, and the Senate is scheduled to consider the issue this fall.

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