Embryonic stem cells may mutate over time, study finds
WASHINGTON -- Human embryonic stem cells, sought by researchers because of a potential to help rejuvenate ailing organs, do not remain as ageless and unblemished as scientists once thought, according to a research report. Like ordinary cells, stem cells accumulate mutations over time, including several that could cause them to become tumors.
The findings, reported yesterday by an international team of scientists, could bolster the positions of 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 human embryos only days old, can be integrated into all kinds of tissues. They divide repeatedly in laboratory dishes, churning out self-replenishing colonies indefinitely. That trait has lent them a reputation as possible fountains of youth.
Researchers hope to harvest batches of the cells periodically from master colonies, and to 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 that had been approved for use by federally funded researchers. The researchers compared the extent of the abnormalities before and after each lineage was subjected to a dozen or more rounds of cell division.
Previous efforts had found little evidence of changes, leading some scientists to conclude the cells were largely protected from the ravages of everyday genetic wear and tear.
But using ''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. Transplanting such cells into a patient could cause more medical problems than they might solve, scientists said.
Chakravarti warned that the work must be confirmed by additional experiments. ''But if it turns out these cells really do become unstable over time," Chakravarti 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. A 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 before using them in treatments, 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; the Senate is scheduled to consider the issue this fall.
