Stem Cells Have Few Mutations

Researchers have found that embryonic stem cells develop a relatively small number of mutations which can be detected by screening. They felt that the mouse embryonic stem cells were actually more genetically stable than some adult cells.
Jay A. Tischfield, a researcher at Rutgers University and a co-author of the study, everybody has assumed that the embryonic stem cell had a mutation rate, we show that it is actually lower than what you find in the adult cells. Peter J. Stambrook, a cell biologist at the University of Cincinnati and a co-author of the study, said that the most common embryonic stem cell mutation found in the mice was the deletion of a chromosome that is replaced by a second copy of the remaining chromosome.

Although the numerical balance of chromosomes is restored by the replacement, the mutation can increase the risk of tumor formation. But this type of mutation is quickly spotted in routine laboratory screening of cells, he said. Starmbrook felt that, it was actually very easy to screen for this mutation and you could then eliminate cells that have undergone this process.

Embryonic stem cells are the master cells for development. They form within a few days of conception and are the primordial cells for all the tissues in the body. Many scientists believe these cells, grow in the laboratory, can be coaxed to transform into liver, heart and other cells that can be used to renew ailing organs.

Many people oppose research with human embryonic stem cells because to isolate them requires the death of an embryo. President Bush last summer issued regulations that would forbid federal funding of human embryonic stem cell research except for cell colonies that already existed. The result is that only about 60 cell colonies are available for federally funded research.

This has prompted widespread research on embryonic stem cell mutations, a key problem in learning how to use the cells for therapy. ``Our study defines one of the problems that can be screened for in embryonic stem cells,'' said Tischfield. The mutation found in the cells ``does not present an insurmountable problem'' in developing ways to use stem cells against disease, he said.

``By knowing what kind of problems that you can find, it allows you to check for them,'' he said. Stambrook noted, however, that the chromosome deletion mutation seems to increase in frequency as a colony of stem cells ages.``These events accumulate as one maintains these cells in culture,'' he said.

Larry Goldstein, a cell biologist at the University of California, San Diego, said the finding that mutations accumulate in a cell culture suggests that it is unlikely that the 78 cell colonies approved for federal funding will be enough to develop medical treatments.

``This paper highlights an issue that we have known about,'' he said. ``Because of the accumulation of mutations in cell lines that have been in culture for a long time, the 78 cell lines are not likely to be maximally beneficial'' for medical treatments.''

Dr. Clive Svendsen, a stem cell researcher at the Waisman Center of the University of Wisconsin, said the Tischfield-Stambrook study ``points out something important to we need to be aware of'' in studying human embryonic stem cells and their possible medical application. But he noted that mouse stem cells are known to be more prone to mutation than are human stem cells and that what is found in mice often does not apply to humans.