Genetic abnormalities found in stem cell lines
People have pinned a lot of hopes on pluripotent stem cells -- which, because of their amazing capacity to morph into other types of cells, have been touted as a potential source for replacement tissues that might someday help reverse spinal cord injuries, Alzheimer’s disease, and even the damage caused by heart attacks.
But so far only two companies have been granted permission by the Food and Drug Administration to move ahead with trials in humans -- Geron Corp., which is testing a treatment for spinal cord injury; and Advanced Cell Technology, which is testing a treatment for macular degeneration.
A new study, published Thursday in the journal Cell Stem Cell, may illustrate part of the reason why. Scientists still haven’t figured out how to make sure most stem cells are safe, and won’t develop into cancer once implanted in patients.
Stem cell scientists at UC San Diego and the Scripps Research Institute used a high-resolution molecular technique called “single nucleotide polymorphism” (SNP) analysis to study stem cell lines. They found that both embryonic stem (ES) cells and induced pluripotent stem (iPS) cells -- adult cells rewound to an embryonic state -- had more genetic abnormalities than other cell types.
ES cells tended to have duplications in the genome, while iPS cells were more likely to have deletions. The scientists located specific regions in the genome where the abnormalities were likeliest to arise. In ES cells, the duplications were near pluripotency-associated genes -- the ones that allow the cells to turn into any other kind of cell in the body. In iPS cells, duplications involved cell proliferation genes, and deletions involved tumor suppressor genes.
The danger of such genetic abnormalities? They are often associated with cancers, said senior author Jeanne F. Loring, in a news release. Loring is director of the Center for Regenerative Medicine at the Scripps Research Institute.
The changes occurred in the cells very rapidly, and would not have been detected by traditional microscopic techniques. “SNP analysis has not been a part of routine monitoring of human ES and iPS cell cultures, but our results suggest that perhaps it should be,” Loring said.
“We don’t know yet what effects, if any, these genetic abnormalities will have on the outcome of basic research studies or clinical applications,” said the study’s lead author, UCSD professor Louise Laurent. “We need to find out.”
Until they do, don’t expect an explosion of ES- or iPS-based cures for disease.
